Deficiency of complement-dependent prevention of immune precipitation in systemic sclerosis.
BACKGROUND
Previous studies have indicated that complement may be activated or inherently abnormal in systemic sclerosis (SSc), and it has been suggested that immune complex deposition plays a part in the microvascular damage of this disease.


OBJECTIVE
To study several aspects of the complement system in 24 patients with SSc.


METHODS
Complement dependent prevention of immune precipitation (PIP) was measured by a sensitive enzyme immunoassay, levels of C1q, C4, and C3 by rocket immunoelectrophoresis, C4 allotypes by high voltage agarose electrophoresis, and C4A, C4B, and C3d by an enzyme linked immunosorbent assay (ELISA).


RESULTS
PIP was markedly decreased in the patients with SSc (p<0.001). Abnormal complement activation was detected in nine patients as raised levels of the complement split product C3d. However, a relation between low PIP and complement activation was not seen. PIP was significantly lower in patients who carried the C4A*Q0 allotype (p=0.03), and a strong correlation was found between PIP and C4A concentration (p<0.00001). The PIP defect may, at least in some patients, be associated with the initial phase of the disease.


CONCLUSIONS
The results show a previously unrecognised functional defect of complement in SSc; the defect correlates with low levels of classical pathway components and, in particular, C4A.
Arason
G J
GJ
Department of Immunology, Landspitali University Hospital, Reykjavík 101, Iceland. garason@landspitali.is
Geirsson
A J
AJ
Kolka
R
R
Víkingsdóttir
T
T
Valdimarsson
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D016022:Case-Control Studies; D015922:Complement C1q / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology*; D003171:Complement Pathway, Classical; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007122:Immunoelectrophoresis / Q000379:methods; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011234:Precipitins / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology*
D003176:Complement C3; D003181:Complement C4; D011234:Precipitins; D015922:Complement C1q