A0002154 32154 No.ofPages:6 SEETHARAMAK Complement:Deficiency Diseases saccharide capsules and be more susceptible to bloodborne C3 deficiency include both an increased susceptibility to bacterial infections.In fact,the prevalence of C4B infection and rheumatic disorders.The infections have deficiency is increased in children with bacteraemia and meningitis included pneumonia,bacteraemia,meningitis and oste ied fogeni C2 deficiency to a moreextensiveclinical picture consistent with systemic upus erythen sus Interestingly.as with some othe om have nts, 10000 in Caucasian populations.The gene for C2 lies of lur within the major histocompatibility complex(MHC)and is ferative glomerulonenhritis has also heen seen in c3 not sumrising that over ofC-deficient individuals C5 deficiency are homozygous for the same mutation.a 28 base pair deletion that results in premature termination of transcrip are unable Complement-medi suc activity.Asexpected,serum opsonic activity is intact since the activation of C3can proceed without the participation rC. nor to the nt identified as C5 deficient hac al pathway s of C2 deficier sequent patients have been ascertained because of either from individuals who have either rheumatic diseases and or an increased susceptibility to infection to individual 2 matic ha ving been ascertained as part of asympto- mily stu de Dt C6 deficiency and aggressive arthritis are less common than in comple- C6 deficiency has been reported in nearly 100 individuals ment-suffciem。 LE patients. lesions are many of whom are of African descent.The most common n in en ash.Patie orm of C6 defici with C2 deficiency and SLE have a lower en prevalence of r it The to their is a marked deficiency of serum bactericidal activity.A ibed C2 subtotal deficiency of C6(C6SD for C6 subtotal rized by s derma tomyositis,anaphylactoid purpura and vasculitis.Ap- otein has a lowe molecular weight and although it can proximately C2-d have incorporated into the membrane attack complex.it ections functions less efficiently encapsulated organisms (e.g.pneumococcus.n he major clinica manifest of complete C6 and meningococcus). While most patients have had meningococcal sepsis and meningitis,others have had disseminated gor ococcal C3 deficiency nfections.Patient with C6SD do not appear to have an increased susceptibility to infection Patients with C3 deficiency generally have less than 1%of C7 deficiency er a rectly dep le i C9 (chemotaxis and bactericidal ac are also markedly reduced.The clinical manifestations of (<1%).Serum bactericidal activity is markedly reduced. ENCYCLOPEDIA OF LIFE SCIENCES/2001Na els netsaccharide capsules and be more susceptible to bloodborne bacterial infections. In fact, the prevalence of C4B deficiency is increased in children with bacteraemia and meningitis. C2 deficiency Genetically determined C2 deficiency is the most common of the inherited complement deficiencies, occurring in 1 in 10 000 in Caucasian populations. The gene for C2 lies within the major histocompatibility complex (MHC) and is associated with a conserved MHC haplotype, HLA-B18, C2*QO, Bf*S, C4A*4, C4B*2 and DR*2. Because of its linkage disequilibrium with the conserved haplotype, it is not surprising that over 95% of C2-deficient individuals are homozygous for the same mutation, a 28 base pair deletion that results in premature termination of transcrip￾tion. Complement-mediated serum activities, such as opsonization and chemotaxis, are present in patients with C2 deficiency, presumably because their alternative path￾way is intact, although they are not generated as quickly nor to the same degree as in individuals with an intact classical pathway. The clinical manifestations of C2 deficiency have varied from individuals who have either rheumatic diseases and/ or an increased susceptibility to infection to individuals who are asymptomatic. Approximately 40% of C2- deficient individuals develop SLE or discoid lupus. Patients with C2 deficiency express many of the character￾istic features of lupus, although severe nephritis, cerebritis and aggressive arthritis are less common than in comple￾ment-sufficient SLE patients. Cutaneous lesions are common in C2-deficient patients with lupus and many have a characteristic annular photosensitive rash. Patients with C2 deficiency and SLE have a lower prevalence of anti-DNA and antinuclear antigen antibodies than do other SLE patients, but their incidence of anti-Ro antibodies is higher. A variety of other rheumatic disorders have also been described in C2 deficiency, including glomerulonephritis, inflammatory bowel disease, derma￾tomyositis, anaphylactoid purpura and vasculitis. Ap￾proximately 50% of C2-deficient patients have an increased susceptibility to bloodborne infections (e.g. sepsis, meningitis, arthritis and osteomyelitis) caused by encapsulated organisms (e.g. pneumococcus, H. influenzae and meningococcus). C3 deficiency Patients with C3 deficiency generally have less than 1% of the normal amount of C3 in their serum. Those serum activities either directly dependent on C3 (opsonization) or indirectly dependent on C3 because of its role in the activation of C5–C9 (chemotaxis and bactericidal activity) are also markedly reduced. The clinical manifestations of C3 deficiency include both an increased susceptibility to infection and rheumatic disorders. The infections have included pneumonia, bacteraemia, meningitis and osteo￾myelitis caused by encapsulated pyogenic bacteria. The rheumatic disorders have varied from limited clinical involvement, such as arthralgias and vasculitic skin rashes, to a more extensive clinical picture consistent with systemic lupus erythematosus. Interestingly, as with some other complement-deficient patients, C3-deficient patients may not have serological evidence of lupus. Membranoproli￾ferative glomerulonephritis has also been seen in C3- deficient patients. The renal disease may reflect the role of C3 in immune complex clearance. C5 deficiency The sera of patients with C5 deficiency are unable to generate normal amounts of chemotactic or bactericidal activity. As expected, serum opsonic activity is intact, since the activation of C3 can proceed without the participation of C5. Although the initial patient identified as C5 deficient had SLE and membranoproliferative glomerulonephritis, sub￾sequent patients have been ascertained because of either meningococcal meningitis or disseminated gonococcal infections. A few C5-deficient patients have been asympto￾matic, having been ascertained as part of family studies. C6 deficiency C6 deficiency has been reported in nearly 100 individuals, many of whom are of African descent. The most common form of C6 deficiency is characterized by absent or nearly absent levels of C6 (5 1% of normal), whether it is assessed immunochemically or functionally. The only abnormality relating to their serum complement system is a marked deficiency of serum bactericidal activity. A subtotal deficiency of C6 (C6SD for C6 subtotal deficiency) has also been described which is characterized by serum levels of C6 that are 1–2% of normal. This truncated C6 protein has a lower molecular weight and although it can be incorporated into the membrane attack complex, it functions less efficiently. The major clinical manifestation of complete C6 deficiency has been disseminated neisserial infections. While most patients have had meningococcal sepsis and meningitis, others have had disseminated gonococcal infections. Patients with C6SD do not appear to have an increased susceptibility to infection. C7 deficiency Only a few patients with C7 deficiency have been identified. Most individuals have severely reduced levels of C7 (5 1%). Serum bactericidal activity is markedly reduced. a2154 No. of Pages: 6 SEETHARAMAK Complement: Deficiency Diseases A0002154 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 3