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Clinico-immunogenetic investigations show that there exists highly significant positive and negative associations of HLA-antigen with chronic glomerulonephritis (CGN). The detected HLA markers of CGN predisposition may appear valuable for grouping subjects at high risk to develop CGN, in prognostication of individual features of CGN running, differential diagnosis and perfection of early therapy.
OBJECTIVE: To assess the longterm outcome of mothers of children with isolated congenital complete heart block (CCHB), and the maternal specific immunoblot pattern and HLA antigens. METHODS: Fifteen mothers of 16 children with isolated CCHB were investigated; their followup extended up to 15.8 years on average after the index delivery. Anti-Ro and La antibodies were detected by counterimmunoelectrophoresis and ELISA; anti-Ro antibodies were studied by immunoblot. HLA typing was done using a microcytotoxicity test. RESULTS: One mother has systemic lupus erythematosus (SLE) before the index delivery. The other mothers developed only minor symptoms (arthralgia, dry eyes and photosensitivity) resembling primary Sjögren's syndrome more than classic lupus. All 15 mothers were anti-Ro and 9 were also anti-La positive, a mean of 12.5 years after the index delivery. Eight mothers reacted with the 52 kDa SSA(Ro) component, and 2 also with the 60 kDa SSA(Ro) component. The prevalence of the DR3 antigen and of the B44/DR5, DR3/DQ2 and A1/Cw7/B8/DR3/DQ2 haplotypes was significantly increased. CONCLUSION: The longterm outcome for the mothers of children with CCHB is more reassuring than generally assumed. All the mothers were anti-Ro positive by sensitive ELISA: Reactivity to the denaturated 52 kDa SSA(Ro) component seems characteristic of these mothers, who presented a particular immunogenetic background.
Primary biliary cirrhosis is a chronic cholestatic disease, thought to be immune-mediated with genetic susceptibility encoded in the major histocompatibility complex. In northern Europeans, the best established associations are with HLA-DR8 and the complement allele, C4B2. These associations could be due to a single susceptibility locus on an extended haplotype linking HLA-DR8 and C4B2 or to both HLA-DR8 and C4B2 independently conferring disease susceptibility. C4B2 genotyping was performed on 64 patients with primary biliary cirrhosis and 61 controls matched for ethnic background and frequency of HLA-DR8. C4B2 was associated with HLA-DR8 (p < 0.05) in PBC. No difference in the frequency of C4B2 was detected between control and disease populations, suggesting that HLA-DR8 and C4B2 are in linkage disequilibrium and that C4B2 is not a susceptibility locus for PBC. Taq I polymorphisms were screened in the disease and control populations with the cosmid probe G91, located midway between the HLA-DR and complement loci. One G91 restriction fragment (G91A) was found to be associated with both HLA-DR8 and C4B2, at equal frequency in health and disease, providing evidence of an HLA-DR8-G91A-C4B2 extended haplotype. The frequency of G91A was the same in the disease and control populations, suggesting that G91A does not confer disease susceptibility. These findings establish G91 as the telomeric boundary for disease susceptibility associated with HLA-DR8, encoded on chromosome six. These studies help define the immunogenetic susceptibility locus for primary biliary cirrhosis.
An immunogenetic investigation was conducted of 82 patients with renal disease. 48 of them had nephrotic syndrome (NS) of different origin (glomerulonephritis, amyloidosis, diabetic glomerulosclerosis). The findings were compared to those obtained at control population studies of 619 healthy residents of St. Petersburg. A statistically significant increase in the incidence of HLA antigens A-10, B-13, B-35, B-41, DR-2, DR-7 and high homozygosity were found in NS patients. Antigen A-2 occurred statistically less frequently. A relative risk (RR) to develop the disease was in all cases > 2. Typing of NS patients and those with high diagnostic titers of antistreptolysin-O revealed in them a significantly higher occurrence (r < 0.01) of A-10 and B-40 antigens compared to controls and NS-free patients. HLA antigens appeared related to morphological variants of glomerulonephritis running with NS. The study results suggest association between genetic, etiological factors and body's response to injury. Feasibility of NS prognosis is reviewed.
The comparative characterization of the level of development of some reproductive qualities of sows of three breeds from five breeding herds of the southern regions of Ukraine was performed in relation to peculiarities of genotypes with respect to some genetic systems of blood groups and serum proteins. Its results favor the complex approach for predicting animal productivity on the basis of data of immunogenetic analysis.
HLA antigens distribution among subgroups of rheumatoid arthritis (RA) patients was compared with reference to the results achieved after the treatment with transfusion of extracorporeally irradiated autologous blood (TEIB). The treatment efficacy was found to be in general 66% and to depend on HLA phenotype, age of the patients, the RA activity. The analysis of associations of clinical significance exhibited by clinical, laboratory and immunogenetic signs made it possible to derive a formula for individual prognostic criterion capable of raising TEIB efficacy to 89%.
OBJECTIVE: The relationship between rheumatoid factor positive (RF+) and rheumatoid factor negative (RF-) rheumatoid arthritis (RA) is controversial. We sought to determine whether the HLA genes conferring susceptibility for erosive RF+RA are also prevalent in patients with erosive RF-RA. METHODS: DNA-based HLA typing for DRB1, DQB1, and DPB1 was performed on 16 consistently RF--patients with erosive RA. RESULTS: Thirteen of 16 (81%) RF-RA patients had the HLA susceptibility genes DRB1 *0401, *0404, or *0101, which are associated with RF+RA, as compared to 46% of normal controls (p = 0.017). By contrast, no associations with HLA-DQB1 and HLA-DPB1 alleles were apparent. CONCLUSION: Specific HLA susceptibility alleles are prevalent in patients with erosive RA, regardless of RF status, suggesting a similar immunogenetic basis for RA in these patients.
Progress in comprehension of the immunogenetics of the HLA-complex and the discovery of new very potent immunosuppressive agents have enabled organ and tissue transplantations to be performed as a relatively routine therapeutic method. Long-term outcome measured as a half-life in kidney transplantations is 25 years among HLA-identical siblings, 12 years in one haplotype-mismatched paternal donors, and 7 years in cadaver transplantation program. The long-term outcome in the latter group can be markedly improved--to as much as 19 years--when six-antigen program is observed (i.e. donor and recipient are identical in HLA-DR, -B, and -A antigens). The survival of patients after bone marrow transplantation (BMT) having as a donor a HLA-identical sibling has improved remarkably, too. However, only about 30 percent of patients who might benefit from a bone marrow transplant have a genotypically. HLA-identical sibling who could be a donor. Transplants from unrelated donors have become therefore an alternative method. To find HLA-matched donors the establishment of large registries are needed. One of them--Them Bone Marrow Donors Worldwide--in Leiden has over 1.2 million of potential donors at the time being (1992).
By using the frequencies of 43-46 antigens of 9-11 genetic blood group systems in 108145 animals the immunogenetic similarity (r +/- m(r)) and the distance (d) between a Swiss brown cattle and other 86 representatives of the Bovinae subfamily were calculated. The position of Swiss brown cattle on a linear model of the Bovinae family was determined. The position has following indexes: r = 0.7816 +/- 0.0197; d = 0.2181. Phylogenesis of 16 cattle breeds reared with participation of the Swiss brown breed was studied. On the dendrogram these breeds formed two clusters and three branches. The clusters at the bottom of the dendrogram (Swiss brown x brown carpathian) and in the middle (ala-tau x caucasian brown) included breeds reared in the foothills and highlands, and the top of the dendrogram is formed by the lebedin, kostroma breeds and the Tajik type of Swiss brown zebu cattle reared in the flat country.
To reveal immunogenetic factors involved in the pathogenesis of rheumatoid arthritis(RA), two hundreds and four unrelated Japanese patients with RA were typed for HLA by both serologic typing and DNA typing using polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Serologic HLA typing data showed that frequencies of HLA-A11, DR4, DR53, and DQ4 were increased and those of DR8, DR52, and DQ1 were decreased in the patient group. The HLA-DNA typing has defined more precisely the disease-associated HLA-class II alleles and revealed that DRB1*0405, DQA1*03, and DQB1*0401 were strongly associated with the disease susceptibility whereas DRB1*0803, DQA1*0103, and DQB1*0601 showed negative association with RA. Comparison of amino acid sequences of DRB1*0405 with other DRB1 alleles suggested that the risk for RA was closely associated with particular amino acid residues of DR beta chain, i. e. glycine residue at the 86th position in addition to the residues between 70th and 74th position. The significant decreased frequency of DRB1*0803 in the DRB1*0405 positive patient group suggests that DRB1*0803 may control resistance to RA as a dominant genetic trait. In addition, the observation that the frequency of DPB1*0201 was increased in the DRB1*0405 negative patient group may indicate that the disease susceptibility to RA is controlled by the HLA-DP region in the minority of the patients. The polymorphism of TAP2 gene and TCR genes showed no significant association with RA, suggesting that the contribution of these genes to the susceptibility is relatively small, if any.
52 patients with primary and 42 with secondary generalized epilepsy at the age of 2-16 years were examined. In all the patients blood content of T- and B-lymphocytes as well as of their subpopulations (T-helpers, T-suppressors) was estimated with the use of monoclonal antibodies. Immunogenetic studies of allogenic lymphocytes were also performed in mixed lymphocyte cultures for proband and mother. There was an increase of CD4/CD8 ratio (T-helper/T-suppressor) as well as elevation of B-lymphocytes level in patients with secondary generalized form of epilepsy. A positive reaction of allogenic lymphocytes from mother and child in mixed cultures was observed in 46 patients with primary generalized epilepsy (88.5%), in 16 cases with progredient disease. In secondary generalized form of epilepsy it occurred in 7 cases only (16.7%). In 28 cases of epilepsy with progredient course not only antiepileptic drugs but also immunomodulators were used with positive effect in 14 patients.
Novel Strategy to identify CTL epitopes called "reverse immunogenetics" was introduced. CTL epitopes were identified as follows; (i) Identification of the motif of HLA class I binding peptides (ii) Selection of sequences matched to the motif of HLA class I binding peptides from HIV proteins and synthesis of peptides (iii) Identification of HLA class I binding peptides by the peptide binding assay (iv) Induction of CTL from PBL of HIV 1 infected individuals by HLA class I binding peptides. Multiple HIV-I epitopes presented by HLA-B35 were identified using this strategy.
Immunogenetic examination comprising determination of erythrocyte antigens (ABO systems and resus-factor) and leukocytes (HLA system) using hemagglutination and compliment-dependent cytotoxicity, respectively, was performed for 138 patients with chronic recurrent pancreatitis, 52 patients with chronic pancreatitis and 456 healthy subjects. Analysis of relations between the above antigens, the disease risk, clinical and laboratory parameters, readings of ultrasound histogram and the efficacy of treatment helped discover not only provoking and protecting genes, but also some pathogenetic mechanisms involved in genetic predisposition. These findings may be used in the choice of treatment policy and to upgrade the significance of prognosis of principal forms of chronic pancreatitis.
Reviews the recent progress in immunopathogenesis, immunogenetics, immunodiagnosis, immunotherapy, and immunoprophylaxis of tuberculosis. The findings of Russian scientists (primarily at the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences) are compatible to the results of medical centers abroad.
Interest in the complexity of the HLA system and its relevance in the selection of unrelated bone marrow donors has had an important impact on our understanding of the immunogenetics of HLA and non-HLA or minor histocompatibility systems. More than 50 genes on the short arm of chromosome 6, which carries the information for HLA, have been identified and there are more to come. HLA-class I and HLA-class II each have more than 200 alleles, and the number is growing. The HLA-C antigens appear to act as targets for natural killer cells. New inroads have been made in the recognition of the minor histocompatibility antigens HA-1 to -5, which can be recognized by cytotoxic T-cell clones and are inherited in a Mendelian fashion. A mismatch for HA-1 might lead to graft-versus-host disease. The introduction of new technologies, especially polymerase chain reaction, has been immensely helpful in mapping the genetic complexity of HLA. Methodology now allows typing for HLA on the level of DNA in a matter of a few hours and is most useful when selecting a suitable bone marrow donor. The new genetic information available makes it clear that many so-called HLA matched unrelated bone marrow transplants performed in the past were actually mismatched. Nevertheless, many of them had a good clinical outcome. It is clear that one of the most important challenges is to determine which mismatched transplants will fare well and which should be avoided. Recent findings in organ transplantation might be helpful here.
The occurrence of multiple primary malignant neoplasms in single individuals is well documented. Although many hypotheses have been advanced to explain this occurrence, there has been no study to determine if a presumed "increased susceptibility to cancer" has an immunogenetic basis. We evaluated the cellular immunity and histocompatibility antigens of 42 patients who had had from two to four multiple primary malignant neoplasms. We failed to demonstrate a preexisting impairment of immunocompetence or abnormal HL-A antigen frequencies in these patients. The occurrence of multiple primary malignant neoplasms in related tissues, eg, lung/larynx/oral cavity, and the occurrence of successive primary malignant neoplasms at a time interval consistent with the patient's being cured of preceding malignant neoplasms suggest that multiple primary malignant neoplasms result from repetitive induction by the same or similar etiologic factors in patients who are cured after treatment of the first malignant neoplasm.
OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familial IIM were compared with those in 181 patients with sporadic IIM. The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 2 families with inclusion body myositis. RESULTS: The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002). CONCLUSION: These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM.
The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic resonance images of the brain and spinal cord were studied in 57 Japanese patients with multiple sclerosis (MS). Twenty-three patients clinically displayed selective involvement of the optic nerve and spinal cord and were classified as having Asian-type MS. The other 34 patients had disseminated central nervous system involvement and were classified as having Western-type MS. Patients with Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but more gadolinium-enhanced spinal cord lesions than did patients with Western-type MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101 allele were associated with Western-type MS (41.2%), but not with either Asian-type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS thus suggests the presence of two etiologically distinct diseases in Asians.