Disease relevance of C4B

• Applications of these vigorously tested techniques may clarify the roles that human C4A and C4B gene-dosage variations play in infectious and autoimmune diseases [1].
• The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity [2].
• Genetic polymorphisms of HLA antigens and HLA-linked serum complement components (C2, C4A, C4B and BF) were investigated in 79 Japanese patients suffering from psoriasis [3].
• Several autoimmune disorders as well as congenital adrenal hyperplasia (CAH) are either associated or closely linked with genetic variants of the fourth component of complement (C4A and C4B) and the enzyme steroid 21-hydroxylase (21-OH) [4].
• Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group [5].

Psychiatry related information on C4B

• In senile dementia of the Alzheimer type, a striking increase in the frequency of the rare C4B locus allele, C4*B2, was apparent, resulting in the high relative risk of RR = 8.8 (p less than 0.0001) for this disorder [6].
• In this study we attempted to confirm the increased incidence of the C4B null allele in autism and investigated the presence of a C4B null allele in two other childhood disorders, attention-deficit hyperactivity disorder and dyslexia (reading disability) [7].
• In contrast to reported findings we failed to find a significant association between C4B2 gene frequency and Alzheimer's dementia [8].

High impact information on C4B

• These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected CH genes [9].
• We propose that the 3'EH-/- mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different CH genes that lie as far as 100 kb upstream of the mutation [9].
• The IgM-bearing B cells carry Cmu genes with rearrangements between VH and JH genes on both chromosomes even though only one chromosome is expressed; clearly, allelic exclusion cannot be explained by the lack of CH gene rearrangement on the nonexpressed chromosome [10].
• CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody [10].
• The histidine at position 1,106(aspartic acid in C4A) first attacks the thioester to form an acyl-imidazole intermediate [11].

Chemical compound and disease context of C4B

• HLA-linked complement markers in Alzheimer's and Parkinson's disease: C4 variant (C4B2) a possible marker for senile dementia of the Alzheimer type [6].
• To evaluate a possible role of major-histocompatibility-complex (MHC)-related immune-response genes for the selective production of drug-induced antibodies, HLA class I (ABC), class II (DR, DQ), class III (BF, C2, C4A, C4B) as well as glyoxalase-1 allotypes were investigated in 26 patients with nomifensine-induced immune hemolytic anemia [12].
• The expression level of CH/71 in E. coli was very high after induction with IPTG [13].

Biological context of C4B

• Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins [1].
• Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex [14].
• A comprehensive series of novel or improved techniques has been developed to determine the total gene number of C4 and the relative dosages of C4A and C4B in a diploid genome [1].
• The gene encoding this protein (CYP21B) and a closely linked pseudogene (CYP21A) have been mapped in the HLA complex on chromosome 6p, adjacent to the complement genes C4B and C4A, about 80 kb from the factor B gene [15].
• The second maternal chromosome, inherited by the unaffected brother, presented an unusual CYP21A gene deletion without a C4A or C4B gene deletion [16].

Anatomical context of C4B

• We also found that serum deficient in C4A or C4B supported binding of CRP and IgG complexes to erythrocytes [17].
• Unequal expression of complement C4A and C4B genes in rheumatoid synovial cells, human monocytoid and hepatoma-derived cell lines [18].
• In order to examine the synthesis, function, and regulation of these two genes independently, cloned C4A and C4B genes were transfected into mouse fibroblast L-cells [19].
• Is decreased blood plasma concentration of the complement C4B protein associated with attention-deficit hyperactivity disorder [20]?
• In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0.51, P = 0.0000004) than C4A [21].

Associations of C4B with chemical compounds

• Analysis of the C4/21-OH genes of patients with the classical (salt-wasting) form of CAH showed that some involve a deletion of the C4B and 21-OHB genes; whereas for two only the 21-OHB gene is deleted, i.e., the C4B gene is present [4].
• Hemolytically inactive C4B complement allotype caused by a proline to leucine mutation in the C5-binding site [22].
• However, irrespective of the amino acid at residue 458, the mutant proteins behaved like their wild-type counterparts with respect to covalent binding to C1-bearing targets, i.e., the C4B recombinants displayed higher binding to sheep and human red cells than did the C4A counterparts [23].
• The serum concentrations of C4A4 were lower than those of C4B2 in serum from 19 individuals homozygous for type I C2 deficiency (p < 0.0002) [24].
• When C3 at 50% or 100% of normal concentrations was added to the serum reagent together with 100% C4A3 or C4B1, the C4B1-opsonized complexes showed more binding than the C4A3-opsonized complexes [25].

Regulatory relationships of C4B

• C4A3 is more effective than C4B1 in its capacity to inhibit the rate of immune precipitate formation in serum and in serum-free reaction mixtures containing C1 and C4 [26].

Other interactions of C4B

• Characterization of a de novo conversion in human complement C4 gene producing a C4B5-like protein [27].
• Studies of the polymorphism of these plasma proteins have shown associations of BfS, C2C, and C4B3 (2.9) with RA [28].
• The C4F and C4S loci are both closely linked to HLA-B [29].
• METHOD: C4B plasma protein levels were studied using an enzyme-linked immunosorbent assay in a group of 23 subjects meeting DSM-III-R criteria for ADHD and a similar number of age- and sex-matched controls [20].
• The affinity of the complex protein S with C4B-binding protein appeared to be five times higher (B1/2max = 0.07 +/- 0.03 mumol/L) [30].

Analytical, diagnostic and therapeutic context of C4B

• Sequence analysis of the C4B genes showed the amino acids LSPVIH at positions 1101 - 1106, S at position 1157, and ADLR at positions 1188 - 1191 [31].
• Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis [3].
• In this report, the tertiary structures of C4A and C4B were compared using near and far-UV circular dichroism, ANS fluorescence, site-specific monoclonal antibodies and isoelectric focusing [32].
• Long-range PCR and PshAI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are C4A [14].
• To directly ascertain whether this single substitution was responsible for the hemolytic defect in C4A6, we have used site-directed mutagenesis to introduce this change into both C4A and C4B cDNA expression plasmids [23].

References