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lüll Involvement of C4 allotypes in the pathogenesis of human diseases Samano ES; Ribeiro Lde M; Gorescu RG; Rocha KC; Grumach ASRev Hosp Clin Fac Med Sao Paulo 2004[Jun]; 59 (3): 138-44The complement system is an important humoral defense mechanism that plays a relevant role against microbial agents, inflammatory response control, and immunocomplex clearance. Classical complement pathway activation is antibody-dependent. The C4 component participates in the initial step of activation, and C4 expression is determined by 2 pairs of allotypes: C4A and C4B. Deficiencies in C4 allotypes have been associated with several diseases. The aim of the present review is evaluate the reported data in the literature regarding specific C4A and C4B deficiencies and characterize their clinical relevance. We searched the MEDLINE and LILACS databases. Papers referring to total C4 deficiency without allotype evaluation and case reports of primary C4 deficiency were not included. Deficiencies in C4 allotypes have been associated with Mycobacterium leprae infection, erythema nodosum, systemic sclerosis with anti-topoisomerase I antibodies, intermediate congenital adrenal hyperplasia with DR5 genotype, diabetes mellitus type 1 with DR3,4 genotype, and diabetes mellitus with antibodies against islet cells. C4 allotype deficiency is also related to C4B deficiency and autoimmune-associated diseases, such as systemic lupus erythematosus, or diseases with an autoimmune component, such as autism. Some reports associate C4A with thyroiditis after delivery as well as limited and systemic sclerosis without anti-topoisomerase I antibodies. However, the studies with C4A and C4B have been concentrated in isolated populations, and some of the studies could not be reproduced by other authors.|Alleles[MESH]|Autoimmune Diseases/genetics/*immunology[MESH]|Complement C4a/*deficiency/genetics[MESH]|Complement C4b/*deficiency/genetics[MESH]|Endocrine System Diseases/genetics/*immunology[MESH]|Haplotypes[MESH]|Humans[MESH]|Major Histocompatibility Complex[MESH]|Mental Disorders/genetics/*immunology[MESH]|Skin Diseases/genetics/*immunology[MESH] |