TY - JOUR
T1 - The NADase enzyme CD38
T2 - An emerging pharmacological target for systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis
AU - Peclat, Thais Ribeiro
AU - Shi, Bo
AU - Varga, John
AU - Chini, Eduardo Nunes
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Purpose of reviewHere 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 findingsIn 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.SummaryRecent 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 treatments.
AB - Purpose of reviewHere 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 findingsIn 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.SummaryRecent 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 treatments.
KW - CD38 (cluster of differentiation 38)
KW - NAD (nicotinamide adenine dinucleotide)
KW - rheumatoid arthritis
KW - systemic lupus erythematous
KW - systemic sclerosis
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U2 - 10.1097/BOR.0000000000000737
DO - 10.1097/BOR.0000000000000737
M3 - Review article
C2 - 32941246
AN - SCOPUS:85092682364
SN - 1040-8711
VL - 32
SP - 488
EP - 496
JO - Current opinion in rheumatology
JF - Current opinion in rheumatology
IS - 6
ER -