RESEARCH - Familial clustering of non-nuclear autoantibodies and C3 and C4 complement components in SLE

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Arthritis Rheum. 2008 Mar 27;58(4):1116-1124

Familial clustering of non-nuclear autoantibodies and C3 and C4

complement components in systemic lupus erythematosus.

Hunnangkul S, Nitsch D, B, Chadha S, on CA, Pessôa-Lopes

P, Norsworthy PJ, MM, P, Mackworth-Young C, Isenberg

DA, Whittaker JC, Vyse TJ.

London School of Hygiene and Tropical Medicine, London, UK.

OBJECTIVE: To determine whether key features of systemic lupus

erythematosus (SLE), namely, production of non-nuclear antibodies

(anti-C1q and anticardiolipin antibodies [aCL]) and depletion of

complement components C3 and C4, aggregate in families. In addition,

we examined relationships between anti-C1q and C3 and C4 levels.

METHODS: The study cohort comprised 1,037 predominantly white (82%)

nuclear families in which at least 1 member had SLE. Associations of

antibody measurements between probands and their unaffected siblings

were examined using parametric and nonparametric analyses, along with

associations between unaffected siblings and their parents. The

heritability of anti-C1q, C3, and C4 was estimated, and

interdependencies between these factors were examined in a regression

model accounting for the family structure of the data set. RESULTS: We

demonstrated associations between siblings for anti-C1q (odds ratio

[OR] 3.74, 95% confidence interval [95% CI] 2.65, 5.28) and IgG and

IgM aCL (OR 4.08, 95% CI 1.83, 5.13 and OR 2.06, 95% CI 1.46, 2.91,

respectively) and, for anti-C1q, association between unaffected

parents and their unaffected offspring (OR 4.34, 95% CI 2.16, 8.72).

We also demonstrated significant heritability of anti-C1q, C3, and C4

( approximately 45%). Anti-C1q was negatively associated with C3 and

C4 in SLE probands but not in their healthy relatives.

CONCLUSION: Non-nuclear antibodies and C3 and C4 cluster within the

families of SLE probands, suggesting that specific autoantibody

formation is partly genetically determined, even if the total genetic

effect in unaffected relatives is insufficient to cause disease.

Anti-C1q antibodies accelerate C3 and C4 depletion in patients with

SLE but have no effect in the absence of disease.

PMID: 18383369

http://www.ncbi.nlm.nih.gov/pubmed/18383369

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