A study of C4AQ0 and MHC haplotypes in Icelandic multicase families with systemic lupus erythematosus

Objective. To study MHC haplotypes and C4AQ0 in Caucasian multicase systemi c lupus erythematosus (SLE) families from Iceland. Methods. Eight families with 26 SLE patients, 98 non-SLE first-degree relat ives, and a control group were studied. For statistical analysis one SLE pa tient and one first-degree relative were randomly chosen from each family. C4 allotyping was performed by protein electrophoresis, HLA typing of class I by the lymphocytotoxicity test, and typing of class II alleles with poly merase chain reaction with sequence specific primers. Results. Six of the 8 families showed a high background of C4A protein defi ciency (C4AQ0) and a significant increase was seen in C4AQ0 in the randomly chosen group of patients. A similar tendency that was statistically nonsig nificant was seen in first-degree relatives. In the SLE patients: C4AQ0 was found on several MHC haplotypes. Waif the patients with C4A protein defici ency carry C4AQ0 on the classical C4A deletion haplotype B8-C4AQ0-C4B1-DR3 or variants of it, and the remaining C4A deficient patients on other non-DR 3 carrying haplotypes. The transmission of C4AQ0 from parents to patients w as in most cases through the family line, although in some instances it ori ginates from outside the multicase SLE family through spouses married into the family. Conclusion. In these Caucasian multicase SLE families from Iceland, C4AQ0 s hows weaker linkage disequilibrium with DR3 than reported in studies on oth er white populations, emphasizing the role of ethnicity. The common factor in the MHC haplotypes studied is C4AQ0, supporting a hypothesis that C4AQ0 may be an independent risk factor for SLE.