Complement and IgG subclasses in agammaglobulinemic patients.
Complement and IgG subclass analysis was performed in six agammaglobulinemic patients suffering from recurrent bacterial infections. Complement analysis included functional activity of the classical (CH50) and the alternative pathway (APH50) of complement, the complement proteins C3, C4, factor B, the regulators C1-inhibitor, factors H and I as well as the C3-derived split product C3dg/C3d. Plasma concentrations of total IgG ranged between < 0.01 and 297 mg/dl. IgM and IgA were almost undetectable. Levels of all IgG subclasses, which in most cases were measurable only by sensitive ELISA, were markedly reduced in all patients. A pronounced activation of the complement system was observed in all patients as revealed by reduced titers of hemolytic function and elevated levels of C3dg/C3d. Despite the fact that complement activation by itself was the major reason for decreased C4 levels, from depressed plasma concentrations of the common allotypic variants C4A and C4B, a heterozygous C4 deficiency could not be excluded in 2/6 patients. Our data clearly show that, by application of sensitive analytical methods, agammaglobulinemic patients vary considerably in their ability to synthesize immunoglobulins. This may, at least in part, explain the heterogeneous pattern of clinical symptoms. The increased susceptibility of agammaglobulinemic patients to bacterial infections is reflected by a highly activated, and thereby depleted complement system.
Grumach
A S
AS
Department of Pediatrics, Faculty of Medicine, University of São Paulo, Brazil.
Kirschfink
M
M
D000293:Adolescent; D000361:Agammaglobulinemia / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation; D003181:Complement C4 / Q000172:deficiency; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008297:Male; D014960:X Chromosome
D003181:Complement C4; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D003165:Complement System Proteins