Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency.
OBJECTIVE
To analyse rheumatological manifestations, organ damage and autoimmune responses in a large cohort of patients (n = 45) with homozygous C2 deficiency (C2D) and long-term follow-up.


METHODS
Medical records were reviewed and were supplemented with a mailed questionnaire for assessment of cardiovascular disease (CVD) risk factors. Organ damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Causes for disability pensions were investigated. Autoantibodies were determined with established methods.


RESULTS
Patients with rheumatological diseases had systemic lupus erythematosus (SLE, n = 12), undifferentiated connective tissue disease (n = 5) or vasculitis (n = 3). Judging from annual SLICC/ACR DI, C2D patients with SLE run a similar risk of development of severe disease as other patients with SLE. An increased rate of CVD was observed not explained by Framingham-related risk factors. Disability pensions were mainly related to rheumatological disease. The prevalence of anti-nuclear antibodies in C2D with SLE and of anti-SS-A was 25% while anti-RNP was found in 45%. Only one patient showed antibodies to dsDNA. Formation of anti-cardiolipin antibodies (aCL) appeared to be increased in C2D despite the absence of an anti-phospholipid syndrome. The prevalence of antibodies to the collagen-like region of C1q (C1qCLR) was also remarkably high and was not related to rheumatological manifestations.


CONCLUSIONS
Severity of SLE in C2D is similar to that of SLE in other patients. Conventional risk factors do not explain the occurrence of CVD in C2D. The high prevalence of aCL and anti-C1qCLR indicates mechanisms through which impaired complement function promotes formation of autoantibodies.
Jönsson
G
G
Department of Infectious Diseases, University Hospital of Lund, SE-221 85, Lund, Sweden. goran.b.jonsson@skane.se
Sjöholm
A G
AG
Truedsson
L
L
Bengtsson
A A
AA
Braconier
J H
JH
Sturfelt
G
G
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D002318:Cardiovascular Diseases / Q000276:immunology; D016009:Chi-Square Distribution; D015922:Complement C1q / Q000276:immunology; D003175:Complement C2 / Q000172:deficiency*; D003240:Connective Tissue Diseases / Q000276:immunology; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000276:immunology*; D018709:Statistics, Nonparametric; D014657:Vasculitis / Q000276:immunology
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D003175:Complement C2; C035356:SS-A antibodies; D015922:Complement C1q