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C A Alper

Publications and source records attributed to C A Alper.

At least 19 recordsLinked to original sources
PubMed1992

The immune response to hepatitis B vaccine in humans: inheritance patterns in families.

We have recently shown that the human antibody response to the hepatitis B virus surface antigen (HBsAg) vaccine is major histocompatibility complex (MHC) associated. In studies of nonresponders to the vaccine, we found an increased incidence of individuals homozygous for human histocompatibility leukocyte antigen (HLA) proteins associated with the extended (conserved) haplotype [HLA-B8,SC01,DR3]. In later prospective vaccination trials, we showed that none of five individuals homozygous for this haplotype developed more than 1,300 radioimmunoassay (RIA) units of antibody (mean, 467 RIA units), while all heterozygotes made at least 2,500 RIA units (mean antibody level, 15,608 units). Our results suggested that [HLA-B8,SC01,DR3] lacks an immune response gene for HBsAg, and that response is inherited in a dominant fashion. To provide further evidence for this hypothesis, we have now analyzed the results of HBsAg immunization in families. 43 members of 10 families were immunized with the hepatitis B vaccine, including seven families where at least one member bore the haplotype [HLA-B8,SC01,DR3], and three families where one member had already received, but failed to respond to, the vaccine. In two of these three families, the presence of [HLA-B8,SC01,DR3] was subsequently found. Of nine MHC-identical sibling pairs in the study, both members of eight pairs had similar antibody responses (five nonresponder and three responder pairs). In all families with such sibling pairs, including the discordant pair, rank-ordering members by antibody level demonstrated that no relative's value came between the sibling pair values. Furthermore, of nine [HLA-B8,SC01,DR3]-haplotype-homozygous individuals, six were nonresponders, and two others had only low-normal responses. [HLA-B8,SC01,DR3]-heterozygous family members always had higher levels of antibody than their homozygous relatives. Linkage analysis of nonresponse to HLA haplotypes revealed a maximum likelihood LOD (logarithm of the odds) score of 6.3 at a recombination fraction of 0.1. The MHC association with lack of antibody response to HBsAg was not seen with tetanus immunization, where 1 of 20 HBsAg responders and 1 of 21 poor or nonresponders had tetanus titers of less than 1:512; both tetanus nonresponders were [HLA-B8,SC01,DR3] heterozygotes. Our results indicate that: (a) response to the HBsAg vaccine is MHC linked, and inherited in a dominant fashion; (b) an abnormal or missing immune response (Ir) gene for HBsAg is a characteristic of most examples of the extended haplotype [HLA-B8,SC01,DR3]; and (c) other haplotypes also have abnormal or missing Ir genes for HBsAg.

Female↗
PubMed1992

HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy.

MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only.

Asthma↗
PubMed1992

Predictability of alloreactivity among unrelated individuals.

Extended haplotypes are specific HLA-B, BF, C2, C4A, C4B and DR allelic combinations that occur at high frequencies and show positive linkage disequilibrium among these highly polymorphic MHC markers. About 30% of all normal caucasian haplotypes are extended, and the matching of two extended haplotypes in unrelated individuals has been shown to match for the determinants of primary mixed lymphocyte reactivity (MLR-I). In this work we report that the matching of one extended haplotype and a serologically defined HLA-DR generic type on the second chromosome in unrelated individuals is associated with the absence of mixed lymphocyte reactivity in 15 to 30% of the cases studied. Our results suggest that, for those individuals who carry either one or two extended haplotypes, it is relatively easy to identify an unrelated MLR-I-matched subject. However, for individuals lacking at least one extended haplotype, it should be difficult to find an MLR-I-matched unrelated subject.

Alleles↗
PubMed1992

Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with type I diabetes.

A significant proportion of relatives of patients with insulin-dependent (type I) diabetes with high titers of cytoplasmic islet cell autoantibodies (ICAs) do not progress to overt diabetes with up to 8 yr of follow-up. This may reflect that follow-up of such relatives has not been long enough to observe diabetes, that despite expression of identical ICAs, some relatives will not progress to diabetes; or that there is heterogeneity in what is identified as ICA. We identified a subset of ICA that was restricted in its species (not reacting with mouse islets) and cell-type reactivity within islets (beta-cell specific). Only one of eight relatives whose sera had the restricted pattern of reactivity progressed to overt diabetes, and on sequential evaluation, all but the one relative who progressed to diabetes have maintained normal first-phase insulin secretion to intravenous glucose. In contrast, by life-table analysis, 70% of relatives expressing nonrestricted ICA became diabetic within 5 yr of follow-up (1 of 8 vs. 16 of 25 diabetic at last follow-up, P less than 0.02). Moreover, preliminary data suggest a significant association of the human leukocyte antigen DQB1*0602 allele of DR2 haplotypes with the restricted ICA pattern (4 of 5 DQB1*0602 restricted vs. 0 nonrestricted ICA, P = 0.006). We propose that expression of a genetically determined restricted ICA pattern confers a markedly lower risk for progression to diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

No independent association between HSP70 gene polymorphism and IDDM.

A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested by several authors. Autoantibodies against HSPs have been associated with such autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD mouse model of diabetes. Moreover, genes for the major 70,000-M(r) HSP (HSP70) are located within the MHC. To investigate a potential association of an HSP70-2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM. With the enzyme PstI, as reported previously, two HSP70-2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele was found more frequently on diabetic haplotypes compared with control haplotypes (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the conservation of alleles on extended haplotypes we previously reported to be associated with diabetes on initial analysis of families. Twenty-three of 26 diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of 9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele (P = 8 x 10(-7) DR3 vs. DR2 haplotypes). The alleles were equally distributed among DR4 haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Conserved, extended MHC haplotypes.

Extended major histocompatibility complex (MHC) haplotypes are fixed conserved regions of the short arm of the sixth human chromosome defined by their HLA-B, complotype (BF, C2, C4A, C4B), HLA-DR alleles. The regions of conservation may extend further. At least a third of normal MHC haplotypes in Caucasians are extended, and they are largely responsible for previously observed linkage disequilibrium in the region. They are relatively population-specific. Their presence has major implications for tissue transplantation, and particularly for the identification of unrelated donor-recipient pairs, since matching for extended haplotypes probably optimizes engraftment in individuals who have them. Even for those who do not, extended haplotypes provide the means for identifying likely MLR-I-negative donor-recipients, and for identifying the genes involved in this function. Extended haplotypes provide most of the markers for HLA-associated autoimmune diseases; like the MHCs of inbred and inbred recombinant strains of mice, they have aided in the analysis of the contribution of specific genes in this region to disease susceptibility and immune functions, particularly the antibody response. Finally, extended haplotypes must be taken into account when considering population genetic questions and when using HLA markers to identify individuals in forensic applications.

Asthma↗
PubMed1991

Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and II and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P less than 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class II allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP.

Eye Diseases↗
PubMed1991

Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.

Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype [HLA-B38, SC21, DR4, DQw8] or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) haplotypes in 25 non-Jewish PV patients, DR4, DQw8 was found in 12 of the patients and DRw6, DQw5 was found in 15. Only 3 patients had neither. Only 1 of the DR4, DQw8 haplotypes was [HLA-B38, SC21, DR4, DQw8] and 2 were HLA-B35, SC31, DR4, DQw8; most were the presumed fragments (SC31, DR4, DQw8) or (SC21, DR4, DQw8) or DR4, DQw8 with some other complotype. Of the patients with DRw6, DQw5, all were DRw14, DQw5, and 6 had a rare Caucasian haplotype, HLA-Bw55, SB45, DRw14, DQw5. Four of 6 of these were found in patients of Italian extraction, as was the 1 normal example. The non-Jewish patients were of more Southern European extraction than our controls. This suggests that there are two major MHC susceptibility alleles in American patients with PV. The more ancient apparently arose on a haplotype in the Jews, HLA-B38(35), SC21(SC31), DR4, DQw8, and spread to other populations largely as D-region segments. The other arose in or near Italy on the haplotype HLA-Bw55, SB45, DRw14, DQw5 and has also partially fragmented so that many patients carry only DRw14, DQw5. The available data do not permit the specific localization of either the DR4, DQw8- or the DRw14, DQw5-linked susceptibility genes.

Alleles↗
PubMed1991

The cellular basis for lack of antibody response to hepatitis B vaccine in humans.

We had previously obtained evidence that among normal subjects the humoral antibody response to hepatitis B surface antigen (HBsAg) was bimodally distributed with about 14% of subjects producing less than 1,000 estimated radioimmunoassay RIA units. From the study of major histocompatibility complex (MHC) markers in the very poor responders who produced less than 36 estimated RIA units of antibody, it appeared that there was an excess of homozygotes for two extended haplotypes [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7]. This finding suggested that a poor response was inherited as a recessive trait requiring nonresponse genes for HBsAg on both MHC haplotypes and was strengthened by finding a much lower antibody response among prospectively immunized homozygotes for [HLA-B8, SC01, DR3] compared with heterozygotes. In the present study, we have analyzed the cellular basis for nonresponse to this antigen by examining antigen-specific proliferation of T cells from responders and nonresponders in the presence and absence of autologous CD8+ (suppressor) cells. Peripheral blood cells from nonresponders to HBsAg failed to undergo a proliferative response to recombinant HBsAg in vitro, whereas cells from responders proliferated vigorously. This failure of cells from nonresponders to proliferate was not reversed in cell mixtures containing CD4+ and antigen-presenting cells devoid of CD8+ cells. There was no difference between responders and nonresponders with respect to the number of circulating T cells or their subsets, or the proliferative response to mitogens such as pokeweed or phytohemagglutinin or another antigen, tetanus toxoid. Our results indicate that our HBsAg nonresponding subjects have a very specific failure in antigen presentation or the stimulation of T helper cells, or both. Our evidence is against specific immune suppression as the basis for their nonresponsiveness. The failure of antigen presentation or T cell help is consistent with recessive inheritance of nonresponsiveness and suggests that response is dominantly inherited.

Antibody Formation↗
PubMed1991

Association of polymorphisms in the HLA-B region with extended haplotypes.

Genomic probes from the HLA-B region of the major histocompatibility complex (MHC) were used to study the association of restriction fragment length polymorphisms (RFLPs) with various MHC alleles, complotypes, and extended haplotypes. The two DNA probes, M20A and R5A, were derived from previously cloned cosmids and are located 38 and 110 kilobases (kb) centromeric to HLA-B, respectively. Five different RFLP variants occurring in five different haplotypic combinations were detected within a panel of 40 homozygous-typing cells and cells from 21 families using Bst EII. In two informative families with HLA-B/DR recombinations the inheritance of the RFLP variants was consistent with their mapping between HLA-B and complotypes. The R5A/M20A haplotypic pattern 6.5 kb/3.0 kb (A) had a normal Caucasian frequency of approximately 0.43 and was found in all independent examples of the extended haplotypes [HLA-B8,SC01,DR3], [HLA-B18,F1C30,DR3], [HLA-Bw62,SC33,DR4], [HLA-B44,SC30,DR4], and [HLA-Bw47,FC91,0,DR7]. The patterns 6.9 kb/3.0 kb (B), 6.5 kb/4.7 kb (C), 1.45 kb/3.0 kb (D), and 6.9 kb/4.7 kb (E) had normal Caucasian frequencies of approximately 0.23, 0.15, 0.15, and 0.04 and were found on all independent examples of [HLA-B38,SC21,DR4], [HLA-Bw57,SC61,DR7], [HLA-B7,SC31,DR2], and [HLA-B44,FC31,DR7], respectively. Individual complotypes or HLA-B alleles which were markers of extended haplotypes showed variable associations. For example, HLA-B7 and the complotype SC31 were associated with all R5A/M20A RFLP haplotypes except haplotype E, although [HLA-B7,SC31,DR7] was associated exclusively with haplotype D. HLA-B27, not known to be part of an extended haplotype, was surprisingly exclusively associated with the 6.5 kb/4.7 kb or C haplotypic pattern in all five instances tested. These findings support the concept of regional conservation of DNA on independent examples of extended haplotypes. The results also further characterize these haplotypes.

Alleles↗
PubMed1991

Decreased inhibition of immune precipitation by sera with the C2 B allotype.

Complement-mediated precipitation inhibiting (CMPI) activity of sera of 5 individuals homozygous for C2 B was compared to that of sera of 20 individuals carrying the common C2 C allotype. Sera with the rare C2 B allotype had a depressed CMPI capacity in both the early (5 min) and the late (60 min) stages of the reaction. We have also compared the CMPI activity of seven homozygous C4A deficient (C4A*Q0) and eight C4B deficient (C4B*Q0) serum samples and did not find significant differences from the controls (no C4 null alleles) in any stage of the reaction. These results indicate that C2 is the critical component in the CMPI reaction of the two constituents of the classical pathway C3 convertase and that C2 B is less active than C2 C.

Antigen-Antibody Reactions↗
PubMed1991

A restriction fragment of the C2 gene is a unique marker for C2 deficiency and the uncommon C2 allele C2*B (a marker for type 1 diabetes).

There are three common C2 protein alleles in caucasians, C2*C, C2*B, and C2*Q0, with allele frequencies of 0.96, 0.03, and 0.01, as well as Sst I RFLP variants of 2.75, 2.7, 2.65, 2.55, and 2.4 kb, with frequencies of 0.017, 0.533, 0.358, 0.017, and 0.075. Thus, C2*C is informatively split by the RFLP. Of 94 nonrandomly ascertained caucasian complotypes, 77 contained C2*C, four contained C2*Q0, and 13 had C2*B. None of the C2*C-containing complotypes carried the 2.75 kb Sst I fragment and all of the complotypes with C2*B or C2*Q0 carried it. All of the C2*Q0 alleles were associated with C4A*4, C4B*2 in the complotype S042 as previously reported. C2*B was usually (9/13) in the complotype SB42, occasionally (1/13 each) in SB45, SB41, SB(4,3)0, and SB31. Thus, the association of the C2 2.75-kb fragment was with C2*B and C2*Q0, not with C4A*4, C4B*2, or even C4A*4 alone. The complotype SC42 was associated with the 2.65-kb Sst I fragment in four of five instances and in a single example with the 2.7-kb fragment. C2*B and C2*Q0 possibly had a common evolutionary ancestor complotype which carried the 2.75-kb Sst I fragment, and BF*S, C4A*4, and C4B*2. C2*B (particularly as the haplotype HLA-Bw62, SB42, DR4) is associated with type 1 diabetes but C2*Q0 is protective.

Alleles↗
PubMed1991

Specific association of HLA-DR4 with increased prevalence and level of insulin autoantibodies in first-degree relatives of patients with type I diabetes.

First-degree relatives of patients with insulin-dependent (type I) diabetes (n = 264 from 106 families) were evaluated with HLA typing and determination of competitive insulin autoantibodies (CIAAs) and islet cell autoantibodies (ICAs). The levels of CIAAs in 30 relatives exceeded our upper limit of normal (greater than or equal to 39 nU/ml), and 30 had high-titer ICAs (greater than or equal to 40 Juvenile Diabetes Foundation units [JDF U]). Eleven of the HLA-typed relatives developed diabetes during follow-up. Twenty-three percent (28 of 123) of the relatives with at least one HLA-DR4 allele were CIAA+ (CIAA greater than or equal to 39 nU/ml) versus 4% (6 of 141) among DR4- relatives (P less than 0.0001). Twenty-one of 22 of the highest CIAA values were all in the DR4+ group (DR4+ vs. DR4-, P = 0.003, Wilcoxon's rank-sum test). HLA-DR3 did not correlate with the level of CIAAs, and neither DR3 nor DR4 correlated with titer of ICAs measured in JDF U. We conclude that, in first-degree relatives of patients with type I diabetes, there is a striking association with HLA-DR4 in both the prevalence of relatives exceeding the normal CIAA range and in the level of CIAAs. These data suggest that a gene on HLA-DR4 haplotypes contributes to the level of anti-insulin autoimmunity, and we hypothesize that DR4-associated diabetes susceptibility, distinct from DR3-associated susceptibility, may be secondary to this influence.

Autoantibodies↗
PubMed1990

The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus.

Previous studies of patients with systemic lupus erythematosus (SLE) have shown an increased frequency of certain major histocompatibility complex (MHC) markers, including HLA-DR2, DR3, and C4AQ0 (C4A-null), in Caucasian patients. However, most of these studies were of randomly selected, unrelated patients; families were not included, and haplotypes were not determined. In order to define more accurately the possible role of MHC genes in lupus susceptibility, HLA-A, B, C, and DR, as well as BF, C2, C4A, C4B, and GLO, markers were determined in 62 Caucasian patients of known ethnic background, and in the members of their families. The distributions of extended haplotypes (fixed combinations of HLA-B, DR, and complotype alleles), fragments thereof, and individual alleles were determined in SLE patients and controls. The MHC distributions in all patients were compared with haplotypes in a normal Caucasian population. There were no statistically significant differences between the frequencies of any MHC marker, fragment, or extended haplotype in the patients compared with the controls. The patients were categorized into 2 groups of European ancestry (English/Irish; other Europeans), and each group was compared with a group of ethnically matched controls. There was a statistically significantly increased frequency of the alleles C4AQ0 and DR3 and the complotype SC01 in SLE patients of English/Irish descent as compared with ethnically matched controls. The increase in C4AQ0 and DR3 could be accounted for by the fact that they were part of the extended haplotype [HLA-B8;SC01;DR3] and/or its fragment (SC01;DR3). No increase in any MHC marker was observed in the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement System Proteins↗
PubMed1990

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus.

Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)--encoded genes. We have used nucleotide sequence analysis to better define the disease-associated MHC alleles. HLA-DR2, DQw1, and especially the rare allele DQ beta 1. AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non-Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQ beta 1.1, the DQ beta 1.AZH, or the DQ beta 1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a "protective" effect.

Alleles↗
PubMed1990

HLA-DQ RFLP variants of five HLA-DQw2-bearing major histocompatibility complex extended haplotypes.

We have analyzed genomic DNA in a large number of independent examples of five HLA-DQw2-bearing extended haplotypes for their associated subtypes by restriction fragment length polymorphism (RFLP) using DRB, DQA, and DQB probes after Taq I and Pst I digestion and Southern blotting. In addition to three previously described HLA-DQw2 subtypes, DQw2a, DQw2b, and DQw2c, we observed a fourth subtype, HLA-DQw2d, characterized by 5.8 kilobase (kb) DRB/Taq I, 2.4, 2.3, and 1.8 kb DQB/Taq I, and 8.0 and 2.3 kb DQA/Pst I fragments. All 22 independent examples of the extended haplotype [HLA-B8, SC01, DR3] carried DQw2a and all 11 independent examples of [HLA-B18, F1C30, DR3] carried DQw2b. In addition, all independent examples (21 and 4, respectively) of two DR7-carrying extended haplotypes, [HLA-B44, FC31, DR7] and [HLA-Bw47, FC91,0,DR7], carried DQw2c and all independent examples of [HLA-Bw57, SC61, DR7] carried DQw2d. Our results show that the DNA in the DR/DQ region of extended haplotypes is relatively fixed and that different DQw2 subtypes characterize different DQw2-bearing extended haplotypes.

Blotting, Southern↗
PubMed1990

Complotypes in individuals of African origin: frequencies and possible extended MHC haplotypes.

We analyzed the frequency distribution of 106 complotypes [four allele sets of the major histocompatibility complex (MHC) genes for the complement proteins factor B, C2, C4A, and C4B] from 32 Black families residing in Boston and Washington, DC. Twenty-five different complotypes were identified, among which there were four complotypes that had not been previously observed in our large database of complotypes compiled from family studies of Boston Caucasians and that are, presumably, unique to individuals of African origin. These four African-derived complotypes are FC(1,90)0, FC63, S1C2, 17, and SC(3,2,90)0. The frequencies of two of these four unique Black complotypes, FC(1,90)0 and FC63, were increased significantly when compared to Caucasians (pcorr less than 0.00042, pcorr = 0.00294, respectively). The complotype FC(1,90)0 was in positive linkage disequilibrium with HLA-DR3 haplotypes containing the B locus antigens Bw42, Bw52, Bw53, and Bw58, while FC63 was associated with HLA-Bw70, -DR5. These findings demonstrate the extensive polymorphism of complotypes in Blacks, and also suggest that it may be possible to define unique extended haplotypes of African origin.

Alleles↗