Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wegener's granulomatosis (WG), characterized by systemic vasculitis and granulomatous inflammation, is a rare chronic rheumatic condition potentially sharing some etiopathological principles with other autoimmune disorders, e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several large association studies have identified genetic risk factors for RA and SLE. Thereof, we have evaluated the relevance of the most promising ones in WG. 22 single nucleotide polymorphisms (SNPs) within or in the vicinity of CCL21, CD40, CDK6, IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/C5 have been genotyped in >600 German WG cases and >800 matched controls. While most polymorphisms did not show suspicious effects on WG susceptibility, SNPs representing TNFAIP3 (rs6922466, p = 0.032, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.7--0.98) and CDK6 (rs42041, p = 0.0201, OR 1.21, 95% CI 1.03-1.43) revealed nominally significant differences in allele distribution. The strongest association was detected for a functionally relevant four SNP haplotype of IRF5, which comprised a protective effect (p = 0.0000897, p (corrected) = 0.0012, OR 0.73, 95% CI 0.62-0.85) similar to those previously seen in RA and SLE. Thus, we suggest that WG, SLE, and RA share some, but not many, genetic risk factors, which supports models of partly overlapping etiopathological mechanisms in these disorders.
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PMID:A functionally relevant IRF5 haplotype is associated with reduced risk to Wegener's granulomatosis. 2004 10

Pathogenic autoantibodies arise in many autoimmune diseases, but it is not understood how the cells making them evade immune checkpoints. Here, single-cell multi-omics analysis demonstrates a shared mechanism with lymphoid malignancy in the formation of public rheumatoid factor autoantibodies responsible for mixed cryoglobulinemic vasculitis. By combining single-cell DNA and RNA sequencing with serum antibody peptide sequencing and antibody synthesis, rare circulating B lymphocytes making pathogenic autoantibodies were found to comprise clonal trees accumulating mutations. Lymphoma driver mutations in genes regulating B cell proliferation and V(D)J mutation (CARD11, TNFAIP3, CCND3, ID3, BTG2, and KLHL6) were present in rogue B cells producing the pathogenic autoantibody. Antibody V(D)J mutations conferred pathogenicity by causing the antigen-bound autoantibodies to undergo phase transition to insoluble aggregates at lower temperatures. These results reveal a pre-neoplastic stage in human lymphomagenesis and a cascade of somatic mutations leading to an iconic pathogenic autoantibody.
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PMID:Lymphoma Driver Mutations in the Pathogenic Evolution of an Iconic Human Autoantibody. 3205 83

Objective: Intestinal Behcet's disease (iBD) is an autoimmune disorder diagnosed by typical intestinal ulcers and systemic Behcet's disease (BD) manifestations. Haploinsufficiency of A20 (HA20) is a recently described autoinflammatory disease with a phenotype resembling BD, caused by heterozygous loss-of-function mutations in TNFAIP3 gene (encoding A20). Methods: We described a 29-year-old female with iBD-like symptoms including relapsing ulceration of intestinal anastomosis, recurrent oral ulcers and vasculitis in extremities. Due to the atypical intestinal ulcers with long segmental involvement and intestinal obstruction, whole exome sequencing (WES) was performed to screen for the underlying genetic defect and the identified gene was confirmed by Sanger sequencing. The expression levels of A20 was evaluated by Western blot. Sanger sequencing and Western blot were also performed in the patient's family members. Results: A heterozygous mutation of TNFAIP3 (c.305A>G, p. Asn 102 Ser) was identified in the patient. The identical TNFAIP3 mutation was also found in her father and brother who had suffered from recurrent oral ulcers since childhood. Functional experiments revealed that the expression of A20 was decreased in the peripheral blood mononuclear cells of the patient and her family members who carried the TNFAIP3 mutation. Conclusion: We described a Chinese patient with a novel heterozygous mutation in TNFAIP3 who developed iBD-like symptoms. We proposed that the TNFAIP3 heterozygous mutation (c.305A>G, p. Asn 102 Ser) with an insufficient expression of A20 may be associated with the iBD phenotype in patients.
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PMID:A20 Haploinsufficiency in a Chinese Patient With Intestinal Behcet's Disease-Like Symptoms: A Case Report. 3271 80