The NADase enzyme CD38: an emerging pharmacological target for systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis

Purpose of review Here we review recent literature on the emerging role of nicotinamide adenine dinucleotide (NAD+) metabolism and its dysfunction via the enzyme CD38 in the pathogenesis of rheumatologic diseases. We evaluate the potential of targeting CD38 to ameliorate NAD+-related metabolic imbalance and tissue dysfunction in the treatment of systemic sclerosis (SSc), systemic lupus erythematous (SLE), and rheumatoid arthritis (RA). Recent findings In this review, we will discuss emerging basic, preclinical, and human data that point to the novel role of CD38 in dysregulated NAD+-homeostasis in SSc, SLE, and RA. In particular, recent studies implicate increased activity of CD38, one of the main enzymes in NAD+ catabolism, in the pathogenesis of persistent systemic fibrosis in SSc, and increased susceptibility of SLE patients to infections. We will also discuss recent studies that demonstrate that a cytotoxic CD38 antibody can promote clearance of plasma cells involved in the generation of RA antibodies. Summary Recent studies identify potential therapeutic approaches for boosting NAD+ to treat rheumatologic diseases including SSc, RA, and SLE, with particular attention to inhibition of CD38 enzymatic activity as a target. Key future directions in the field include the determination of the cell-type specificity and role of CD38 enzymatic activity versus CD38 structural roles in human diseases, as well as the indicators and potential side effects of CD38-targeted tre...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by John Varga Source Type: research

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Publication date: Available online 1 October 2019Source: Best Practice &Research Clinical RheumatologyAuthor(s): Francisca Alves, Margarida GonçaloAbstractSkin lesions occur, often at very early stages, in many of the most frequent inflammatory rheumatic diseases such as in systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), Sjögren's syndrome, rheumatoid arthritis (RA), and psoriatic arthritis.It is important to recognize the different specific cutaneous lesions in SLE (e.g., “butterfly” rash in acute, annular or psoriasiform photosensitive lesions in the subacut...
Source: Best Practice and Research Clinical Rheumatology - Category: Rheumatology Source Type: research
This article presents an overview on recent advances in optical non-invasive diagnostics of the peripheral hemodynamics of the upper and lower limbs in rheumatological and endocrinological profile patients. Among these are laser Doppler flowmetry (LDF), tissue reflectance oximetry (TRO), pulse oximetry (PO) and fluorescent spectroscopy (FS). The laser Doppler flowmetry method allows for investigating the blood flow in the microcirculatory bed in vivo. The method is based on probing the tissue with laser radiation and analyzing back reflected from the tissue radiation partially scattered from moving red blood cells (Bonner...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion Trochlear pain (trochleodynia) is becoming recognized as a set of disorders that can present in isolation or concomitantly with co-existing migraines, tension-type headaches, or other headache disorders, possibly explaining subpar symptom control in a small but significant number of individuals globally. Trochleodynia features unilateral periocular pain that may involve the ipsilateral hemicranium. Pain exacerbation occurs with trochlear palpation and supraduction of the affected eye especially in the adducted position. Trochleodynia may respond to oral NSAIDs if symptoms are mild and of recent onset. While ora...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
ConclusionOverlap myositis stands out as a distinct entity as compared to PM and DM, featuring more extramuscular involvement and more severe infections. Close monitoring is recommended in this subset for early detection and treatment of possible complications.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Authors: van Roon AM, Huisman CC, van Roon AM, Zhang D, Stel AJ, Smit AJ, Bootsma H, Mulder DJ Abstract OBJECTIVE: To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). METHODS: NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity
Source: Journal of Rheumatology - Category: Rheumatology Tags: J Rheumatol Source Type: research
Conclusions Although rheumatic diseases are noted at a high rate in north Cyprus, there is no associated HCV infection.
Source: The Egyptian Rheumatologist - Category: Rheumatology Source Type: research
Conclusions Most patients with JMCTD had active disease and organ damage after a mean follow-up of 16.2 years. Active disease was associated with higher anti-ribonucleoprotein antibody levels and positive RF. The presence of RF at diagnosis predicted persistent disease activity.
Source: Annals of the Rheumatic Diseases - Category: Rheumatology Authors: Tags: Immunology (including allergy), Muscle disease, Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis, Systemic lupus erythematosus Clinical and epidemiological research Source Type: research
BackgroundIndirect immunofluorescence plays a major role in the detection of antinuclear antibodies (ANAs) and follow‐up of their titers in the context of connective tissue diseases. Given the numerous unfavorable features of the conventional manual reading of HEP2 slides (need of time and expert morphologists for the reading, lack of standardization, subjectivity of the interpretation), the biomedical industry has developed automated techniques of slide preparation and microscope reading. MethodsWe collected 49 sera beforehand analyzed by the conventional reading of slides. They were prepared again by QUANTA‐Lyser®...
Source: Journal of Clinical Laboratory Analysis - Category: Laboratory Medicine Authors: Tags: Research Article Source Type: research
CONCLUSION: CMR can reveal myocardial lesions in MCTD patients with cardiac symptoms including myocardial infarction, inflammation, diffuse subendocardial fibrosis and diffuse perfusion defects, necessitating further cardiac investigation and/or treatment. PMID: 26728774 [PubMed - as supplied by publisher]
Source: Inflammation and Allergy Drug Targets - Category: Allergy & Immunology Authors: Tags: Inflamm Allergy Drug Targets Source Type: research
I used to enjoy cold weather and cold-weather activities. Not anymore. These days I find it harder and harder to keep my hands warm when I’m outside, even with an excellent pair of gloves. Sometimes my fingers turn white and become numb. Those are the hallmarks of Raynaud’s syndrome (or disease or phenomenon). Named after the French physician who first described it in 1862, Raynaud’s is a problem in the body’s arteries. In most people with Raynaud’s, small arteries that bring oxygen-rich blood to the fingers spasm and close down in response to cold or stress. This reduces or cuts off blood flo...
Source: New Harvard Health Information - Category: Consumer Health News Authors: Tags: Men's Health Pain Management Women's Health cold hands Raynaud's syndrome Source Type: news
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