title: An aggressive form of polyarticular arthritis in a man with CD154 mutation (X-linked hyper-IgM syndrome).
abstract: Hyper-IgM syndrome (HIM) is a rare immunodeficiency disorder that has been associated with the development of symptoms and clinical features characteristic of rheumatoid arthritis (RA). We describe a patient with HIM and severe erosive arthritis with prominent nodules in the absence of detectable serum rheumatoid factor. Because HIM results from defects in either T cell CD154 (CD40 ligand) expression or abnormal CD40 signaling, the molecular basis of the patient's disease was analyzed. Activated CD4+ T cells failed to express surface CD154 protein, and molecular analysis of CD154 complementary DNA revealed a nucleotide transversion resulting in the nonconservative amino acid substitution G-D at amino acid 257. This case indicates that defective CD154-dependent CD40 signaling can be associated with susceptibility to a severe inflammatory arthritis that has both similarities to and differences from idiopathic RA.
authors.affiliation: Columbia University, New York, New York 10032, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Webster
authors.forename: A Y
authors.initials: AY
authors.lastname: Khakoo
authors.forename: W J
authors.initials: WJ
authors.lastname: Mackus
authors.forename: M
authors.initials: M
authors.lastname: Karpusas
authors.forename: D W
authors.initials: DW
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Davidson
authors.forename: C L
authors.initials: CL
authors.lastname: Christian
authors.forename: S
authors.initials: S
authors.lastname: Lederman
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D018076:DNA, Complementary / Q000032:analysis; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011859:Radiography; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D023201:CD40 Ligand