Silica exposure and chronic virus infection synergistically promote lupus-like systemic autoimmunity in mice with low genetic predisposition.
Abstract Considerable evidence indicates that autoimmune disease expression depends on both genetic and environmental factors. Among potential environmental triggers, occupational airway exposure to crystalline silica and virus infections have been linked to lupus and other autoimmune diseases in both humans and mouse models. Here, we hypothesized that combined silica and virus exposures synergize and induce autoimmune manifestations more effectively than single exposures to either of these factors, particularly in individuals with low genetic predisposition. Accordingly, infection with the model murine pathogen l...
Source: Clinical Immunology - June 5, 2019 Category: Allergy & Immunology Authors: Gonzalez-Quintial R, Mayeux JM, Kono DH, Theofilopoulos AN, Pollard KM, Baccala R Tags: Clin Immunol Source Type: research

News and meta-analysis regarding anti-Beta 2 glycoprotein I antibodies and their determination.
Abstract Recent advances allow us to propose antibodies targeting beta-2-glycoprotein I (β2-GPI) as the most specific antibodies associated with anti-phospholipid syndrome (APS). Therefore, there is now a crucial need for powerful biological assays to adequately monitor them. It is well established that these antibodies recognize mainly cryptic epitopes, which requires a great deal of consideration in the choice of laboratory tests to identify these antibodies. To this end, an update on the pathophysiological role of β2-GPI and a meta-analysis were conducted providing an overview of the current progress ...
Source: Clinical Immunology - June 4, 2019 Category: Allergy & Immunology Authors: Bettacchioli E, Nafai S, Yves R Tags: Clin Immunol Source Type: research

Serum leptin levels correlate negatively with the capacity of vitamin D to modulate the in vitro cytokines production by CD4+ T cells in asthmatic patients.
o CAM Abstract Both obesity and low vitamin D levels have been associated with allergic asthma (AA) severity. In the present study, severity of AA was associated with obesity but to the in vitro IgE production. In those patients, higher levels of IL-5, IL-6 and IL-17 were quantified in CD4+ T-cell cultures as compared with patients with mild and moderate AA. In addition, the lowest IL-10 levels were detected in the cell cultures from patients with a worse prognosis. Interestingly, the occurrence of AA elevates the plasma levels of leptin, and this adipokine was positively correlated with the release of IL-5, IL-6 ...
Source: Clinical Immunology - June 4, 2019 Category: Allergy & Immunology Authors: Dias ASO, Santos ICL, Delphim L, Fernandes G, Endlich LR, Cafasso MOSD, Maranhão AL, da Silva SR, Andrade RM, Agrawal A, Linhares UC, Bento CAM Tags: Clin Immunol Source Type: research

Evaluation of the frequency of invariant natural killer T (iNKT) cells in nasal polyps.
Abstract Nasal polyps (NP) are associated with inflamed mucosa of unknown etiology. The role of T cells in nasal polyposis is unclear. Invariant natural killer T cells (iNKT) can promote Th2 responses and have been implicated in some types of asthma. As there are shared inflammatory pathways involved in asthma and NPs, we evaluated the frequency of iNKT in 17 patients with NPs, but without asthma. A median of 6% polyp cells were T lymphocytes, of which iNKT were 0 to 2.38% (mean 0.674%). In the matched group (n = 10), iNKT in NPs was significantly higher than PBMCs (1.057% vs 0.155%, P 
Source: Clinical Immunology - May 29, 2019 Category: Allergy & Immunology Authors: Fereidouni M, Derakhshani A, Yue S, Nasseri S, Hosseini RF, Bakhshaee M, Vahidian F, Exley MA Tags: Clin Immunol Source Type: research

Epidermal growth factor receptor mimotope alleviates renal fibrosis in murine unilateral ureteral obstruction model.
Abstract Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In current study, we sought to observe whether the active immunization induced by the EGFR mimotope could ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F...
Source: Clinical Immunology - May 29, 2019 Category: Allergy & Immunology Authors: Yang L, Yuan H, Yu Y, Yu N, Lin L, Niu J, Gu Y Tags: Clin Immunol Source Type: research

iNKT cells and hematopoietic stem cell transplantation: Two-phase activation of iNKT cells may improve outcome.
Abstract Invariant natural killer T cells (iNKT) produce large amounts of different cytokines which can influence differentiation, polarization and activation of immune cells, particularly NK and T cells. iNKT have been shown to suppress GvHD and promote anti-tumor and anti-pathogen immunity. There are highly specific and safe synthetic ligands such as alpha-galactosylceramide (α-GalCer) and C20:2 which activate iNKT cells toward relatively Th1 and Th2 pathways, respectively. Bone marrow transplantation (BMT) or 'hematopoietic stem cell transplantation' (HSCT) is effective for leukemia and lymphoma through '...
Source: Clinical Immunology - May 22, 2019 Category: Allergy & Immunology Authors: Derakhshani A, Fereidouni M, Exley MA Tags: Clin Immunol Source Type: research

Interleukin 28 is a potential therapeutic target for sepsis.
This study defines IL-28 as a detrimental mediator during sepsis and identifies a potential therapeutic target for the immune therapy in sepsis. PMID: 31121287 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - May 20, 2019 Category: Allergy & Immunology Authors: Luo Q, Liu Y, Liu S, Yin Y, Xu B, Cao J Tags: Clin Immunol Source Type: research

Delay expression of NKp30 on NK cells correlates with long-term mycophenolate mofetil treatment and higher EBV viremia post allogenic hematological stem cells transplantation.
Abstract Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in graft-versus-host disease prophylaxis because of its inhibitory function on T cells and B cells. However, the effect of MMF on natural killer cell reconstitution after allogenic hematological transplantation is largely unknown. The present study examined the effects of different MMF administration durations after haploidentical allo-HSCT on NK cell reconstitution. Ninety patients were enrolled in this study and defined into two groups in term of MMF duration. We found that MMF patients in the long-term MMF group were associat...
Source: Clinical Immunology - May 18, 2019 Category: Allergy & Immunology Authors: Yu X, Cao X, Yan H, Luo XY, Zhao X, Sun Y, Wang Y, Xu L, Zhang X, Chang Y, Huang X, Zhao X Tags: Clin Immunol Source Type: research

Cis-regulatory genetic variants in the CCR5 gene and natural HIV-1 control in black South Africans.
Abstract Studies have investigated CCR5 haplotypes (HHA, HHB, HHC, HHD, HHE, HHF*1, HHF*2, HHG*1, HHG*2), defined by seven 5'UTR single nucleotide polymorphisms (SNPs), CCR2-V64I and CCR5Δ32, in HIV-1 disease. CCR5 cis-regulatory regions were sequenced, CCR2-V64I and CCR5Δ32 genotyped, and compared in HIV-1-infected black South Africans: 71 HIV-1 controllers (23 elite controllers, 37 viraemic controllers (VCs), 11 high viral load long-term non-progressors) and 74 progressors. The HHE haplotype and 3'UTR +2919 T > G SNP heterozygosity were underrepresented in total controllers and VCs vs. progr...
Source: Clinical Immunology - May 14, 2019 Category: Allergy & Immunology Authors: Koor GW, Paximadis M, Picton ACP, Karatas F, Loubser SA, He W, Ahuja SK, Chaisson RE, Martinson N, Ebrahim O, Tiemessen CT Tags: Clin Immunol Source Type: research

Interference of canakinumab with commercial IL-1 β ELISAs.
Interference of canakinumab with commercial IL-1β ELISAs. Clin Immunol. 2019 May 13;: Authors: Linge M, Hedrich CM, Rösen-Wolff A, Winkler S PMID: 31096037 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - May 13, 2019 Category: Allergy & Immunology Authors: Linge M, Hedrich CM, Rösen-Wolff A, Winkler S Tags: Clin Immunol Source Type: research

Candidiasis associated with very early onset inflammatory bowel disease: First IL10RB deficient case from the National Iranian Registry and review of the literature.
In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease. PMID: 31096038 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - May 13, 2019 Category: Allergy & Immunology Authors: Yazdani R, Moazzami B, Madani P, Behniafard N, Azizi G, Aflatoonian M, Abolhassani H, Aghamohammadi A Tags: Clin Immunol Source Type: research

When neonatal inflammation does not mean infection: An early-onset mevalonate kinase deficiency with interstitial lung disease.
We report here a case of mevalonate kinase deficiency (MKD) that presented at birth with mild symptoms and signs suggestive for a perinatal infection, together with the uncommon finding of interstitial lung disease. An extensive diagnostic work-up, performed after ineffective antibiotic treatment, demonstrated high levels of mevalonic acid in urine (7024 mM/M of creatinine, normal value  T (p.T237S) homozygous mutation in the MVK gene, consistent with MKD. Treatment with anakinra led to a prompt resolution of symptoms and a sharp drop in serum inflammatory markers. The patient is now six months-old, currently undergoin...
Source: Clinical Immunology - May 13, 2019 Category: Allergy & Immunology Authors: Pietrasanta C, Minoia F, Torreggiani S, Ronchi A, Gattorno M, Volpi S, Ceccherini I, Mosca F, Filocamo G, Pugni L Tags: Clin Immunol Source Type: research

Inhibition of ROCK activity regulates the balance of Th1, Th17 and Treg cells in myasthenia gravis.
Abstract Aberrant ROCK activation has been found in patients with several autoimmune diseases, but the role of ROCK in myasthenia gravis (MG) has not yet been clearly investigated. Here, we demonstrated that ROCK activity was significantly higher in peripheral blood mononuclear cells (PBMCs) from MG patients. ROCK inhibitor Fasudil down-regulated the proportions of Th1 and Th17 cells in PBMCs of MG patients in vitro. Intraperitoneal injection of Fasudil ameliorated the severity of experimental autoimmune myasthenia gravis (EAMG) rats and restored the balance of Th1/Th2/Th17/Treg subsets. Furthermore, Fasudil inhib...
Source: Clinical Immunology - May 9, 2019 Category: Allergy & Immunology Authors: Song J, Xi JY, Yu WB, Yan C, Luo SS, Zhou L, Zhu WH, Lu JH, Dong Q, Xiao BG, Zhao CB Tags: Clin Immunol Source Type: research

M2a and M2b macrophages predominate in kidney tissues and M2 subpopulations were associated with the severity of disease of IgAN patients.
In this study, renal samples from 49 IgAN patients were detected by immunofluorescence. The markers of M2 macrophages, including M2a (CD206+/CD68+), M2b (CD86+/CD68+) and M2c (CD163+/CD68+) were identified. We found M2a and M2b macrophages were the predominant subpopulations in kidney tissues of IgAN. M2a macrophages were mainly distributed in tubulointerstitium with renal lesions like segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis. However, there were larger numbers of M2c in glomeruli with minor lesions. Moreover, M2a and M2c macrophages were inversely correlated with the clinical and pathologic f...
Source: Clinical Immunology - May 9, 2019 Category: Allergy & Immunology Authors: Hu W, Lin J, Lian X, Yu F, Liu W, Wu Y, Fang X, Liang X, Hao W Tags: Clin Immunol Source Type: research

The exosome as a novel predictive/diagnostic biomarker of rejection in the field of transplantation.
Abstract Finding a non-invasive biomarker to monitor allograft status after transplantation could contribute to better control of the post-transplant status of transplant recipients and, if possible, could be used instead of invasive biopsy for proving rejection. On the other hand, reducing the dosage of immunosuppression or stopping lifelong use of them because of their severe side effects is an important goal in order to dispose of their severe side effects. The ability of exosomes as a biomarker of rejection and as a therapeutic strategy was investigated in the human kidney, heart, and lung transplantation or i...
Source: Clinical Immunology - May 8, 2019 Category: Allergy & Immunology Authors: Mirzakhani M, Mohammadnia-Afrouzi M, Shahbazi M, Mirhosseini SA, Hosseini HM, Amani J Tags: Clin Immunol Source Type: research

Heterozygous activating mutation in RAC2 causes infantile-onset combined immunodeficiency with susceptibility to viral infections.
va OV Abstract Here we describe a 10-year-old girl with combined immunodeficiency presenting as recurring chest infections, lung disease and herpetic skin infections. The patient experienced two hematopoietic stem cell transplantations and despite full chimerism, she developed bone marrow aplasia due to adenovirus infection and died at post-transplant day 86. Immunologic investigation revealed low numbers of TRECs/KRECs, a severe reduction of memory B cells, absence of isohemagglutinins, and low IgG levels. Whole exome sequencing (WES) identified a novel heterozygous mutation in RAC2(c.275A > C, p.N92 T)....
Source: Clinical Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Sharapova SO, Haapaniemi E, Sakovich IS, Kostyuchenko LV, Donkó A, Dulau-Florea A, Malko O, Bondarenko AV, Stegantseva MV, Leto TL, Uygun V, Karasu GT, Holland SM, Hsu AP, Aleinikova OV Tags: Clin Immunol Source Type: research

Cellular immune responses against natural human papillomavirus infections among men in Kisumu, Kenya.
Abstract Human papillomavirus (HPV) is associated with ano-genital and cervical cancer. Persistence of oncogenic HPV genotypes is a requirement for development and progression of malignancies. Although,>70% of women clear incident HPV infections, data on natural history and HPV immunology among men is limited. To evaluate cell-mediated immune responses to natural HPV infections among men, we assessed cytokine responses on PBMCs collected from men with persistent or cleared HPV. Men with HPV clearance and those with HPV persistence had increased odds (6-times and 3-times respectively) of mounting cytokine respon...
Source: Clinical Immunology - May 2, 2019 Category: Allergy & Immunology Authors: Ondondo RO, Bukusi EA, Ng'ang'a ZW, Kiptoo M, Mpoke S Tags: Clin Immunol Source Type: research

Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma.
Abstract T-cell lymphomas include diverse malignancies. They are rare, some have low survival rates and they lack curative therapies. The aim of this work was to assess whether employing the TLR7 agonist imiquimod and the T-cell costimulatory molecule CD40 or the combination of both as adjuvants of a cell lysate vaccine could enhance the antitumor immune response using a murine T-cell lymphoma model. Immunization with LBC-lysate and imiquimod protected almost all vaccinated animals. A specific humoral and a Th1-type cellular immunity were induced in mice that rejected the lymphoma, characterized by an elevated num...
Source: Clinical Immunology - April 29, 2019 Category: Allergy & Immunology Authors: Sciullo PD, Menay F, Cocozza F, Gravisaco MJ, Waldner CI, Mongini C Tags: Clin Immunol Source Type: research

Persisting enteropathy and disturbed adaptive mucosal immunity due to MHC class II deficiency.
We describe multifaceted disturbance of adaptive mucosal immunity in MHC II deficient patients suffering from enteropathy. HLA-DR and Ii expression on enterocytes is not restored by HSCT. This may account for increased susceptibility to enteric infections and intestinal inflammation leading to prolonged enteropathy reported in MHC II deficient patients. PMID: 31028919 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 24, 2019 Category: Allergy & Immunology Authors: Posovszky C, Sirin M, Jacobsen E, Lorenz M, Schwarz K, Schmidt-Choudhury A, Rothoeft T, Schuetz C, Hönig M, Debatin KM, Schulz A, Möller P, Barth TF Tags: Clin Immunol Source Type: research

Bone marrow transplantation with Favorable outcome in three patients with LPS-responsive beige-like anchor (LRBA) deficiency.
PMID: 31026575 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 23, 2019 Category: Allergy & Immunology Authors: Okur FV, Kuskonmaz B, Cagdas D, Tezcan I, Uckan-Cetinkaya D Tags: Clin Immunol Source Type: research

Sjogren's syndrome: An update on disease pathogenesis, clinical manifestations and treatment.
PMID: 31022578 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 22, 2019 Category: Allergy & Immunology Authors: Vivino F, Bunya VY, Massaro-Giordano G, Johr CR, Giattino SL, Schorpion A, Shafer B, Peck A, Sivils K, Rasmussen A, Chiorini JA, He J, Ambrus JL Tags: Clin Immunol Source Type: research

Two paternal mosaicism of mutation in ELANE causing severe congenital neutropenia exhibit normal neutrophil morphology and ROS production.
Abstract Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted from fractionated peripheral blood mononuclear cells (PBMCs) and fingernails obtained from both fathers did harbor the mutation, suggesting mosaicism. Granulocytes isolated from the patients displayed significantly weaker ionomycin-induced intracellular reactive ox...
Source: Clinical Immunology - April 19, 2019 Category: Allergy & Immunology Authors: Liu Q, Zhang L, Shu Z, Ding Y, Tang XM, Zhao XD Tags: Clin Immunol Source Type: research

Treatment of murine lupus with TIGIT-Ig.
In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases. PMID: 31005675 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 18, 2019 Category: Allergy & Immunology Authors: Liu S, Sun L, Wang C, Cui Y, Ling Y, Li T, Lin F, Fu W, Ding M, Zhang S, Lei C, Hu S Tags: Clin Immunol Source Type: research

Diminished cytolytic activity of γδ T cells with reduced DNAM-1 expression in neuroblastoma patients.
Diminished cytolytic activity of γδ T cells with reduced DNAM-1 expression in neuroblastoma patients. Clin Immunol. 2019 Apr 15;: Authors: Wang X, Mou W, Han W, Xi Y, Chen X, Zhang H, Qin H, Wang H, Ma X, Gui J Abstract Neuroblastoma is one of the children's malignant tumors with poor prognosis, as well as high recurrence and metastasis rates after surgical removal and chemotherapy. γδ T-cell based immunotherapy receives increasing attention thanks to their strong cytolytic activity to tumor cells. Our previous data revealed a significant increase in circulating γδ ...
Source: Clinical Immunology - April 15, 2019 Category: Allergy & Immunology Authors: Wang X, Mou W, Han W, Xi Y, Chen X, Zhang H, Qin H, Wang H, Ma X, Gui J Tags: Clin Immunol Source Type: research

MCC950 blocks enhanced interleukin-1 β production in patients with NLRP3 low penetrance variants.
CONCLUSION: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1β release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies. PMID: 30974290 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 8, 2019 Category: Allergy & Immunology Authors: Schuh E, Groß CJ, Wagner D, Schlüter M, Groß O, Kümpfel T Tags: Clin Immunol Source Type: research

Pathogenic roles of anti-C1q antibodies in recurrent pregnancy loss.
In conclusion, our study reveals an association between the prevalence of anti-C1q and RPL. Additionally, our murine model has indicated that anti-C1q can induce reproductive failure, which might be ameliorated by therapy targeting the C5-C5aR axis. PMID: 30974291 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 8, 2019 Category: Allergy & Immunology Authors: Ohmura K, Oku K, Kitaori T, Amengual O, Hisada R, Kanda M, Shimizu Y, Fujieda Y, Kato M, Bohgaki T, Horita T, Yasuda S, Sugiura-Ogasawara M, Atsumi T Tags: Clin Immunol Source Type: research

Characteristics of regulatory T-cell populations before and after Ty21a typhoid vaccination in children and adults.
Abstract Typhoid fever, caused by the pathogen Salmonella enterica serovar Typhi (S. Typhi), is a serious global health concern. Challenge studies with wild type S. Typhi identified associations between gut-homing regulatory T cells (Treg) and development of typhoid disease. Whether oral live-attenuated Ty21a vaccination induces gut-homing Treg remains unclear. Here, we analyze pediatric and adult Treg pre- and post-Ty21a vaccination in an autologous S. Typhi-antigen presentation model to address this knowledge gap. We show that peripheral memory Treg populations change from childhood to adulthood, but not followi...
Source: Clinical Immunology - April 3, 2019 Category: Allergy & Immunology Authors: Rudolph ME, McArthur MA, Magder LS, Barnes RS, Chen WH, Sztein MB Tags: Clin Immunol Source Type: research

Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency.
In conclusion, pathogenic stop variants in the ARD of NFKB2 can cause 'infection-only' CVID with an abnormal B-cell phenotype and a variable clinical penetrance. PMID: 30953794 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 3, 2019 Category: Allergy & Immunology Authors: Tuijnenburg P, Allen HL, de Bree GJ, Savic S, Jansen MH, Stockdale C, Simeoni I, Ten Berge IJM, van Leeuwen EMM, BioResource NIHR, Thaventiran JE, Kuijpers TW Tags: Clin Immunol Source Type: research

Identification of autoantibodies using human proteome microarrays in patients with IPEX syndrome.
Abstract Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is one of the inborn errors of immunity, characterized by impaired function of the regulatory T cells. Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. The comprehensive analysis for autoantibodies using human proteome microarrays in the four patients with IPEX syndrome was performed. The numbers of the highly expressed autoantibody showing relative log2 ratios greater than 1 were 1876, 513, 234 and 831 (mean: 864), respectively. Some novel autoantibodies which coul...
Source: Clinical Immunology - April 2, 2019 Category: Allergy & Immunology Authors: Hoshino A, Kanegane H, Nishi M, Tsuge I, Tokuda K, Kobayashi I, Imai K, Morio T, Takagi M Tags: Clin Immunol Source Type: research

Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results.
CONCLUSIONS: In this large-scale study, we demonstrate that routine SCID screening is feasible and effective. This screening offers the additional benefit of aiding in the diagnosis of non-SCID lymphopenia. Economic evaluation allowed us to calculate the cost per test. Newborn screening may also prevent death by SCID before any curative treatment can be administered. The difference in cost between screened and control children could not be ascertained because of the very low numbers and death of one of the children tested. PMID: 30946917 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - April 1, 2019 Category: Allergy & Immunology Authors: Thomas C, Durand-Zaleski I, Frenkiel J, Mirallié S, Léger A, Cheillan D, Picard C, Mahlaoui N, Riche VP, Roussey M, Sébille V, Rabetrano H, Dert C, Fischer A, Audrain M Tags: Clin Immunol Source Type: research

DNA damage accumulation, defective chromatin organization and deficient DNA repair capacity in patients with rheumatoid arthritis.
Abstract We investigated the DNA damage response and repair network in 18 patients with active rheumatoid arthritis and tested the hypothesis that treatment influences this network. A 3-fold increase of endogenous DNA damage (single- and double-strand breaks) was detected in patient-derived peripheral blood mononuclear cells than controls (alkaline comet assay; mean ± SD Olive Tail Moment of 11.8 ± 7.3 versus 4.3 ± 2.2, p 
Source: Clinical Immunology - March 28, 2019 Category: Allergy & Immunology Authors: Souliotis VL, Vlachogiannis NI, Pappa M, Argyriou A, Sfikakis PP Tags: Clin Immunol Source Type: research

Innate lymphoid cell disturbance with increase in ILC1 in systemic lupus erythematosus.
Abstract The innate lymphoid cell (ILC) is a group of effector cells with diverse important cellular functions in both health and disease states. In comparison with healthy controls, there were increases in circulating ILC in SLE patients. The proportion of ILC1 significantly increased with significant decreases of ILC2 in SLE patients and ILC3 in SLE patients with moderate to severe activity. IL-12, IL-18, IL-25, IL-33, IL-23, IL-1β and IFN-γ were significantly increased in SLE patients. Moreover, IL-12, IL-18 and IL-1β but not IFN-γ correlated significantly with SLEDAI. Successful treatment...
Source: Clinical Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Guo C, Zhou M, Zhao S, Huang Y, Wang S, Fu R, Li M, Zhang T, Gaskin F, Yang N, Fu SM Tags: Clin Immunol Source Type: research

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases.
Abstract BACKGROUND: We investigated the pattern of reported immune diseases in the ASIA registry. METHODS: Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed. RESULTS: The patient mean age was 43 ± 17 years and 89% were female. Within the reported immune diseases 69% were well defined autoimmune diseases (autoimmune, autoinflammation, and mixed pattern diseases). Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher that autoinflammatory disorders (92.7% vs 5.8%, respectively, p 
Source: Clinical Immunology - March 25, 2019 Category: Allergy & Immunology Authors: Watad A, Bragazzi NL, McGonagle D, Adawi M, Bridgewood C, Damiani G, Alijotas-Reig J, Esteve-Valverde E, Quaresma M, Amital H, Shoenfeld Y Tags: Clin Immunol Source Type: research

The inhibitory receptors on NK cells and CTLs are upregulated in adult and adolescent patients with secondary hemophagocytic lymphohistiocytosis.
Abstract Hemophagocytic lymphohistiocytosis (HLH) includes primary HLH (pHLH) and secondary HLH (sHLH). Mutations that cause abnormal functions in natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are frequently identified in pHLH. However, why NK cells and CTLs exhibit abnormal functions in sHLH remains unclear. Here, we demonstrated that NK cells in sHLH exhibited a high expression of inhibitory receptor NKG2A and a low expression of activating receptor NKG2D. Besides, the expression of HLA-E on lymphocyte, the adaptor of NKG2A on NK cells, was elevated in sHLH. Moreover, CTLs in sHLH patients express...
Source: Clinical Immunology - March 23, 2019 Category: Allergy & Immunology Authors: Gao Z, Wang Y, Wang J, Zhang J, Wang Z Tags: Clin Immunol Source Type: research

Activated γδ T cells exhibit cytotoxicity and the capacity for viral clearance in patients with acute hepatitis B.
Activated γδ T cells exhibit cytotoxicity and the capacity for viral clearance in patients with acute hepatitis B. Clin Immunol. 2019 Mar 23;: Authors: Jia ZH, Li YY, Wang JY, Zhang JY, Huang A, Guo XD, Zhu ZY, Wangx FS, Wu XL Abstract γδ T cells are a unique population of lymphocytes that have regulatory roles in patients with chronic hepatitis B (CHB); however, their role in acute hepatitis B (AHB) infection remains unclear. Phenotype and function of γδ T cells were analyzed in 29 AHB patients, 28 CHB patients, and 30 healthy controls (HCs) using immunofunctional ...
Source: Clinical Immunology - March 23, 2019 Category: Allergy & Immunology Authors: Jia ZH, Li YY, Wang JY, Zhang JY, Huang A, Guo XD, Zhu ZY, Wangx FS, Wu XL Tags: Clin Immunol Source Type: research

Rethinking newborn screening for severe combined immunodeficiency: Lessons from an international partnership for patients with primary immunodeficiencies in Pakistan.
PMID: 30858051 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - March 8, 2019 Category: Allergy & Immunology Authors: Wallace JG, Tipu HN, Stafstrom K, Alosaimi MF, Massaad MJ, Bainter W, Geha RS, Chou J Tags: Clin Immunol Source Type: research

Cell mediated immune responses elicited in volunteers following immunization with candidate live oral Salmonella enterica serovar Paratyphi A attenuated vaccine strain CVD 1902.
Abstract The incidence of Salmonella enterica serovar Paratyphi A (PA) infection is on the rise and no licensed vaccines are available. We evaluated cell mediated immune (CMI) responses elicited in volunteers following immunization with a single dose (109 or 1010 cfu) of a novel attenuated live oral PA-vaccine strain (CVD 1902). Results showed increases in PA-lipopolysaccharide-specific IgG- and/or IgA B-memory cells and production of IFN-γ, TNF-α, IL-10, IL-23 and RANTES following stimulation with PA-antigens by peripheral blood mononuclear cells obtained 28 days post immunization. Flow cytometry ...
Source: Clinical Immunology - March 5, 2019 Category: Allergy & Immunology Authors: Wahid R, Kotloff KL, Levine MM, Sztein MB Tags: Clin Immunol Source Type: research

Repository corticotropin injection reverses critical elements of the TLR9/B cell receptor activation response in human B cells in vitro.
Abstract We sought evidence for direct effects of repository corticotropin (RCI; an FDA-approved treatment for selected cases of SLE) on isolated human B lymphocytes activated by engagement of TLR9 and B cell receptors. ODN 2395/αIgM treatment was found to result in induction of 162 distinct mRNAs and suppression of 80 mRNAs at 24 h. RCI treatment resulted in suppression of 14 of the ODN 2395/αIgM -induced mRNAs (mean suppression to 23.6 ± 3.1% of stimulated value). The RCI-suppressed mRNAs included two critical regulators of class switch recombination, AICDA and BATF. RCI treatment also r...
Source: Clinical Immunology - March 4, 2019 Category: Allergy & Immunology Authors: Olsen NJ, Benko AL, McAloose CA, Becker PM, Wright D, Sunyer T, Kawasawa YI, Kovacs WJ Tags: Clin Immunol Source Type: research

Crosstalk between macrophage and T cell in atherosclerosis: Potential therapeutic targets for cardiovascular diseases.
PMID: 30844443 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - March 4, 2019 Category: Allergy & Immunology Authors: Song M, Xu S, Zhong A, Zhang J Tags: Clin Immunol Source Type: research

Compendium of synovial signatures identifies pathologic characteristics for predicting treatment response in rheumatoid arthritis patients.
Abstract Rheumatoid arthritis (RA) is therapeutically challenging due to patient heterogeneity and variability. Herein we describe a novel integration of RA synovial genome-scale transcriptomic profiling of different patient cohorts that can be used to provide predictive insights on drug responses. A normalized compendium consisting of 256 RA synovial samples that cover an intersection of 11,769 genes from 11 datasets was build and compared with similar datasets derived from OA patients and healthy controls. Differentially expression genes (DEGs) that were identified in three independent methods were fed into func...
Source: Clinical Immunology - March 1, 2019 Category: Allergy & Immunology Authors: Kim KJ, Kim M, Adamopoulos I, Tagkopoulos I Tags: Clin Immunol Source Type: research

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort.
We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (
Source: Clinical Immunology - February 25, 2019 Category: Allergy & Immunology Authors: Nabatanzi R, Bayigga L, Cose S, Rowland-Jones S, Canderan G, Joloba M, Nakanjako D Tags: Clin Immunol Source Type: research

Initial safety analysis of a randomized phase II trial of nelipepimut-S  + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors.
We report the initial safety interim analysis of a phase II trial that enrolled patients with HER2 low-expressing (IHC 1+/2+) breast cancer who were clinically disease-free after standard therapy. Patients were randomized to receive the HER2-peptide vaccine nelipepimut-S + GM-CSF with trastuzumab (vaccine arm) or trastuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analysis that occurred after enrollment of 150 patients showed no significant differences in toxicity between the two arms, including cardiac toxicity. The clinical efficacy of this combination will be reported 6 months after the ...
Source: Clinical Immunology - February 25, 2019 Category: Allergy & Immunology Authors: Travis CG, Peace Kaitlin M, Holmes Jarrod P, Vreeland Timothy J, Hale Diane F, Herbert Garth S, Litton Jennifer K, Murthy Rashmi K, Jason L, People George E, Mittendorf Elizabeth A Tags: Clin Immunol Source Type: research

Identification and mutational analysis of continuous, immunodominant epitopes of the major oyster allergen Crag 1.
Abstract Shellfish, including oysters, often cause allergic reactions in children and adults. Oysters are inevitably consumed because of its delicacy and nutritional benefit, leading to frequent occurrence of severe clinical symptoms observed in patients with oyster hypersensitivity. We aimed to identify the immunodominant epitopes of oyster tropomyosin and crucial amino acids for IgE binding, which will help us to further understand the immunochemical characteristics of Cra g 1. The potential epitopes were predicted by immunoinformatics tools and the resultant immunodominant epitopes were identified by inhibition...
Source: Clinical Immunology - February 23, 2019 Category: Allergy & Immunology Authors: Fang L, Li G, Zhang J, Gu R, Cai M, Lu J Tags: Clin Immunol Source Type: research

Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations.
Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations. Clin Immunol. 2019 Feb 15;: Authors: Tometten I, Felgentreff K, Hönig M, Hauck F, Albert MH, Niehues T, Perez R, Ghosh S, Picard C, Stary J, Formankova R, Worth A, Soler-Palacín P, García-Prat M, Allende LM, Gonzalez-Granado LI, Stepensky P, Di Cesare S, Scarselli A, Cancrini C, Speckmann C, Gilmour K, Notarangelo L, Ehl S, Rohr J Abstract Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. I...
Source: Clinical Immunology - February 15, 2019 Category: Allergy & Immunology Authors: Tometten I, Felgentreff K, Hönig M, Hauck F, Albert MH, Niehues T, Perez R, Ghosh S, Picard C, Stary J, Formankova R, Worth A, Soler-Palacín P, García-Prat M, Allende LM, Gonzalez-Granado LI, Stepensky P, Di Cesare S, Scarselli A, Cancrini C, Speckmann Tags: Clin Immunol Source Type: research

Stratum corneum interleukin-33 expressions correlate with the degree of lichenification and pruritus in atopic dermatitis lesions.
PMID: 30772598 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - February 14, 2019 Category: Allergy & Immunology Authors: Nakamura N, Tamagawa-Mineoka R, Yasuike R, Masuda K, Matsunaka H, Murakami Y, Yokosawa E, Katoh N Tags: Clin Immunol Source Type: research

Cytokines, growth factors and proteases in medium and large vessel vasculitis.
Abstract Giant cell arteritis and Takayasu arteritis are autoimmune vasculitides that cause aneurysm formation and tissue infarction. Extravascular inflammation consists of an intense acute phase response. Deeper understanding of pathogenic events in the vessel wall has highlighted the loss of tissue protective mechanisms, the intrusion of immune cells into "forbidden territory", and the autonomy of self-renewing vasculitic infiltrates. Adventitial vasa vasora critically control vessel wall access and drive differentiation of tissue-invasive T cells. Selected T cells establish tissue residency and build ...
Source: Clinical Immunology - February 14, 2019 Category: Allergy & Immunology Authors: Weyand CM, Watanabe R, Zhang H, Akiyama M, Berry GJ, Goronzy JJ Tags: Clin Immunol Source Type: research

Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis.
Abstract Systemic sclerosis (SSc) is a systemic disease characterized by vasculopathy, progressive fibrosis and autoimmune activation. Tryptophan (Trp) metabolism has been linked to altered immune cell function and to malignancy. We have investigated the role of Trp metabolic pathway in SSc measuring serum Trp, Kynurenine (Kyn) and Trp/Kyn ratio in a cohort of 97 SSc patients and 10 healthy controls. Association with disease characteristics was evaluated. We found that Trp levels in SSc patients were significantly lower compared to HCs. We also found that patients with diffuse cutaneous (dcSSc) had lower levels of...
Source: Clinical Immunology - February 13, 2019 Category: Allergy & Immunology Authors: Campochiaro C, Lytton S, Nihtyanova S, Fuchs D, Ong VH, Denton CP Tags: Clin Immunol Source Type: research

BCG-induced formation of neutrophil extracellular traps play an important role in bladder cancer treatment.
In conclusion, we demonstrated a novel immunoregulatory role for NETs in the early stages of BCG immunotherapy. PMID: 30771501 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - February 13, 2019 Category: Allergy & Immunology Authors: Liu K, Sun E, Lei M, Li L, Gao J, Nian X, Wang L Tags: Clin Immunol Source Type: research

CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface.
Abstract CD25 deficiency is a very rare autosomal recessive disorder that shows a clinical phenotype highly overlapping IPEX syndrome with an increased susceptibility to viral, bacterial, and fungal infections. It is due to mutations in the IL2Rα gene that codes for the α subunit of the IL2 receptor complex. Here we report the characterization of a novel IL2Rα gene mutation leading to a severe protein conformational alteration that abrogates its cell surface expression in a child presenting with early-onset IPEX-like disorder. Cytofluorimetric analysis revealed the total absence of CD25 cell surf...
Source: Clinical Immunology - February 8, 2019 Category: Allergy & Immunology Authors: Vignoli M, Mannurita SC, Fioravanti A, Tumino M, Grassi A, Guariso G, Favre C, D'Elios MM, Gambineri E Tags: Clin Immunol Source Type: research

Novel multiple heterozygous NUDT15 variants cause an azathioprine-induced severe leukopenia in a patient with systemic lupus erythematosus.
PMID: 30742971 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - February 8, 2019 Category: Allergy & Immunology Authors: Otsuka M, Koga T, Sumiyoshi R, Fukukawa K, Okamoto M, Endo Y, Tsuji S, Takatani A, Shimizu T, Igawa T, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Kawakami A Tags: Clin Immunol Source Type: research