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J R Batchelor

Publications and source records attributed to J R Batchelor.

At least 91 records · Page 5Linked to original sources
PubMed1987

Family study of the major histocompatibility complex in HLA DR3 negative patients with systemic lupus erythematosus.

Susceptibility to systemic lupus erythematosus (SLE) is known to be governed by genes in the HLA region of the 6th chromosome. From previous studies it has not been possible to distinguish between the effects of null genes for the complement component C4 and HLA-DR3, because of the marked linkage disequilibrium between DR3 and a null allele of C4A (C4A QO) in caucasoid populations. We report here an immunogenetic study of 44 cases of SLE, selected because they were DR3 negative. Eighteen of the 30 Caucasoid cases (60%) had extended HLA haplotypes with a C4 null allele, compared with 22 of 60 (37%) of a control panel of 60 DR3 negative normal Caucasoid subjects. This difference is significant (chi 2 = 4.41; 0.05 greater than P greater than 0.01). Of 14 non-caucasoid patients analysed, 10 had a C4 null allele. It is concluded that the null alleles of the C4 A and B genes are themselves directly responsible for conferring susceptibility to SLE.

Alleles↗
PubMed1987

HLA genetic determinants in familial MS. A study from the Grampian region of Scotland.

Fourteen multiplex MS families, 9 single-case MS families and 11 normal families from the Grampian region of North-East Scotland were studied. The prevalence rate of MS for individuals in multiplex families was calculated at 809/100,000; 4.5 times the prevalence rate for the general population in this region. The distribution of shared haplotypes in 12 affected and 19 unaffected sib-pair comparisons did not differ significantly from that expected by chance. Furthermore there was no evidence that homozygosity of a particular HLA gene was required for increased susceptibility to the disease. HLA-B7, C4A3, C4B1, BfS, HLA-DR2, HLA-DQw1 was the commonest haplotype accounting for 18.9% and 24.2% of parental haplotypes from multiplex and single-case families, respectively, compared with 2.3% of parental haplotypes from control families (p less than 0.05 and p less than 0.01, respectively). No significant differences were observed in the frequencies of complement gene polymorphisms (Factor B and C4). The data suggests that a MS susceptibility gene exists, in the HLA complex, and is in closest linkage disequilibrium with the HLA-D region; although other factors, environmental and/or independent genetic loci, may have an important influence.

HLA Antigens↗
PubMed1986

HLA haplotypes with C4B5; evidence for further allelic heterogeneity.

Twenty-three individuals from various disease groups and normal controls were identified by immunofixation with anti-C4, C4-dependent lysis, determination of Rg (Rodgers) and Ch (Chido) phenotypes, and immunoblotting with C4-specific mouse monoclonal antibody. We found that one haplotype predominates with the C4B*5 allele, HLA-A11, B22(55), Cw3, Bf*S, C4A*4B*5, which also carries the Ch1,-2, 3 haplotype. The B5 allotype was also found with HLA-B60, HLA-B35 in Caucasoids, and HLA-B18 in non-Caucasoids; these carried the Ch-1, -2, -3 haplotype. Our results are in accord with an earlier report of two B5 subtypes, B5Rg+ and B5Rg- (Roos et al. 1984). The specificity of the mouse monoclonal antibodies IC4 and 2B12 had been previously related to C4A and C4B, respectively, but our results suggest that they relate more closely to Rg and Ch determinants.

Alleles↗
PubMed1986

Gm allotypes in multiple sclerosis: influence susceptibility in HLA-DQwl-positive patients from the North-East of Scotland.

From the Grampian region of Scotland, 198 patients with MS and 128 normal individuals were typed for allotypes of the Gm system which encode for the constant region of IgG heavy chains. No significant independent association between a given Gm allotype or phenotype and susceptibility to MS was observed for the group of patients from this region. This was also the case when patients were classified according to sex, clinical course, and disease progression. However, a significant association was found between the Gm phenotype, Gm (3;5, 10, 11, 13, 14), and HLA DQwl in patients with MS. The relative risk of developing MS for individuals who carried both Gm (3;5,10, 11,13,14) and HLA DQwl was nearly five times greater than for individuals with neither determinant. These findings suggest that in the presence of HLA DQwl, genes associated with the Gm (3;5,10,11,13,14) phenotype have an important contributory influence on susceptibility to MS. The additive effects of Gm and HLA on susceptibility to MS would be one possible reason for the lack of a complete association between MS and a single genetic locus.

Gene Frequency↗
PubMed1986

Viral infection in patients with multiple sclerosis and HLA-DR matched controls.

Retrospective comparisons of the prevalence and age, where appropriate, of some childhood infectious illnesses and vaccinations, together with serological evidence for exposure to 16 viruses, many of which have previously been implicated in the aetiology of multiple sclerosis (MS) were made in 177 patients with acute optic neuritis, other recent isolated demyelinating episodes or established MS and 164 controls. The expected high frequency of HLA-DR2 in patients with demyelinating disease was matched by preselection of normal controls with this antigen (DR2+); the remaining individuals were classified as HLA-DR2 negative/DR3 positive (DR3+) or HLA-DR2 and 3 negative (DR2/3 -). Cases were compared with controls, collectively and in analyses restricted to each genetic group; these comparisons were repeated considering the three categories of patients with demyelination and two control populations separately. All DR2+, DR3+ and DR2/3 - individuals were compared in a single analysis to assess the effect of HLA type itself on the results. Patients with demyelinating disease had rubella and measles at a later age and reported mumps infection more frequently than controls. Age of typhoid vaccination and duration of exposure to domestic dogs was higher in all cases than controls. Age of measles and mumps, but not rubella, was higher in DR2+ cases than controls; but differences were not observed in the other genetic groups. Higher rubella antibody titres were present in all cases than controls and in analyses confined to DR2+ individuals in whom higher Epstein Barr virus antibody titres were also present. Measles haemagglutination inhibition and parainfluenza I antibody titres were increased and influenza A antibodies detected less frequently in all patients with optic neuritis and those with DR2 compared with appropriate controls; influenza B antibody titres were lower in all DR2+ cases than controls. Higher adenovirus and varicella zoster antibody titres were present in DR2/3- patients with demyelination and other neurological diseases compared with normal controls. Overall, older age of infection and higher antibody titres were observed more often in patients with optic neuritis, in particular DR2+ cases, than other individuals with demyelination or controls. Our serological results are consistent with the presence of abnormal HLA-immunological reactivity in patients with MS but cannot be explained only by an effect of DR type itself; age at which susceptible individuals develop some common childhood infections may also influence the subsequent development of the disease.

Adult↗
PubMed1986

HLA frequency and haplotype analysis in a family study of adult onset rheumatoid arthritis.

Twenty-five families with probands who have rheumatoid arthritis (RA) were studied for clinical evidence of disease and for HLA status. This confirmed an association between RA and DR4 in 19/25 probands (76 per cent, p = 0.008). These 19 probands carried 24 haplotypes which contained DR4. There was no significant increase of DR4 haplotypes bearing B15(Bw62) or B44 when compared with published control haplotype data. The rare complement allele C4 B3 was detected as part of the extended haplotype A2 Cw3 B15(Bw62) DR4 C4 A*3B*3 in three probands with severe RA. Further studies to examine disease severity and autoantibody expression are in progress.

Arthritis, Rheumatoid↗
PubMed1986

Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia.

We treated 14 patients by transplantation of marrow from unrelated volunteer donors. Eight patients had severe aplastic anemia, 3 had chronic granulocytic leukemia, and 3 had Fanconi's anemia. The results are compared with those of a group of 14 similar patients transplanted concurrently from human leukocyte antigen (HLA)-mismatched family members: Sustained engraftment was achieved in 8 of 14 patients in both groups; one additional patient survived with autologous marrow reconstitution following an unrelated donor transplant. In the unrelated donor group, 6 of 9 evaluable patients developed grade III through IV acute graft-v-host disease, as compared with 4 of 9 patients after family-mismatched transplants. Overall survival was similar in the two groups. In the unrelated donor group 4 of 14 (29%) patients survived (median survival 1,299 days) as compared with 5 of 14 (36%) in the mismatched-family donor group (median survival 808 days). In both groups, patients with HLA phenotypically matched donors fared better than those with donors who were mismatched for one or more HLA antigen. Of the patients transplanted from HLA phenotypically matched donors 6 of 12 patients (50%) survived, as compared with 3 of 16 patients (19%) transplanted from HLA-mismatched donors. We conclude that unrelated donor bone marrow transplantation (BMT) should be considered in those cases of leukemia or bone marrow failure in which the chance of cure using conventional therapy is remote and a HLA genotypically or phenotypically matched family donor is not available.

Anemia, Aplastic↗
PubMed1985

Mechanisms underlying continued survival of rat kidney allografts after a short period of chemical immunosuppression.

Experiments have been carried out to investigate whether the continued survival of rat kidney allografts induced by two different methods-namely, immunological enhancement or a limited course of drug treatment with cyclosporine or cyclophosphamide, is maintained by similar mechanisms. (AS X AUG)F1 or AUG strain kidneys were transplanted to AS recipients that were treated for 14 days with cyclosporine or cyclophosphamide. The limited course of drug treatments induced indefinitely prolonged, or very extended, allograft survival. Long-surviving F1 kidney grafts were retransplanted into naive AS recipients, and by functioning for more than 100 days proved, like enhanced grafts, to be less immunogenic than normal (AS X AUG)F1 kidneys. Very prolonged survival of homozygous, incompatible AUG kidneys was only observed after the cyclosporine drug regimen-and when these grafts were retransplanted to naive second AS recipients, acute or chronic rejection ensued. However, the rejection was prevented if spleen cells from the first AS recipient were adoptively transferred to the second AS recipient at the time of retransplantation. It was concluded that suppressor cells must be present in the transferred spleen cell populations. The experiments show that, as in the case of immunological enhancement, very prolonged allograft survival brought about by a short course of immunosuppressive drug treatment is accompanied by reduction in graft immunogenicity, and by the induction of suppressor cells.

Animals↗
PubMed1985

HLA-typing in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a disease of the mouth and oropharynx characterised by progressive deposition of collagen leading to severe limitation of movement of the jaw in advanced cases. It is almost completely confined to inhabitants of, or migrants from India who chew 'betel nut'. The histopathological and clinical features suggest that autoimmune mechanisms may be involved. Because all chronic autoimmune diseases show disturbance in the frequencies of HLA antigens, we have HLA typed 50 OSF patients and a similar number of healthy subjects of the same ethnic origin. Raised frequencies of A10 and DR3 were observed. The results support the concept that OSF is a chronic autoimmune disease, initiated by constituents of betel nut, and occurring in genetically susceptible individuals. Genes situated in the HLA region are important determinants of genetic susceptibility in OSF.

Autoimmune Diseases↗
PubMed1984

Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma.

Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response-associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.

Biopterins↗
PubMed1984

The influence of HLA-linked genes on the severity of anti-GBM antibody-mediated nephritis.

Thirty-nine Caucasian patients with glomerulonephritis caused by autoantibodies to glomerular basement membrane (GBM) were studied. They were segregated into three groups depending on presentation: Group 1 (19 patients) were anuric or oliguric, group 2 (13 patients) had rapidly deteriorating renal function but were not oliguric, and group 3 (seven patients) had stable renal function. The incidence of HLA-DR2 was greatly increased; it was present in 34 of 38 patients in whom DR antigens were identified compared to 43 of 154 controls (Pc = 0.63 X 10(-8), relative risk 36, etiological fraction 0.86). The incidence of HLA-B7 was also increased; present in 23 of 39 patients and 43 of 193 controls (Pc = 0.26 X 10(-4), relative risk 5.0, etiological fraction 0.43). These data were analyzed for a third order association between HLA-DR2, HLA-B7, and anti-GBM disease. Such an association was probable for patients in group 1 (P = 0.27 X 10(-6), likely for those in group 2 (P = 0.024) but unlikely for patients in group 3 (P = 0.62) suggesting HLA-B7-associated genes influence severity. Clinical results from a subset of the patients referred directly on presentation showed that patients who inherited HLA-B7 together with DR2 had significantly higher plasma creatinines, a greater proportion of glomeruli surrounded by crescents and a worse prognosis. Despite this there was little difference in severity of their lung disease.

Adolescent↗
PubMed1984

Suppressor cells and their role in the survival of immunologically enhanced rat kidney allografts.

A search has been made for suppressor cells in the spleens of AS rats bearing long-surviving, enhanced AUG strain kidney allografts. The assay consisted of an adoptive transfer of splenocytes from AS rats with enhanced AUG kidneys to normal AS rats that also received test grafts of AUG kidneys. The critical feature of the AUG kidney test grafts was that the native population of passenger cells had been replaced by AS passenger cells--thus reducing, but not eliminating, immunogenicity of the graft. With this assay, it was shown that 2.7-3.5 X 10(8) spleen cells transferred substantial and statistically significant suppression of graft rejection. Suppression was also transferred by spleen cells that did not adhere to nylon wool. It is concluded that suppressor cells are one of the mechanisms ensuring continued survival of enhanced kidney allografts.

Animals↗
PubMed1984

HLA DR antigens and disease expression in rheumatoid arthritis.

Ninety-four patients with rheumatoid arthritis who possessed one or more of the HLA DR alloantigens 2, 3, or 4 were studied to investigate the genetic influence on disease severity and prognosis. In those with a disease duration of less than 10 years radiological damage was less in patients with DR2 than in those without this antigen. When current joint scores were compared, patients with this antigen had less evidence of disease than patients with DR3 or 4, DR3 patients having the highest scores. The presence of nodules and Sjögren's syndrome were less common in the DR2 patients. Variability in response to disease modifying drugs according to the patient's HLA DR antigen status may explain these differences. It is concluded, however, that possession of HLA DR2 may be an indicator of good prognosis in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1983

Histocompatibility testing in patients with carcinoma of the bladder.

A number of disease states have been found to have a positive association with certain HLA antigens. Weak associations have been described for a number of cancers. Seventy patients with transitional cell carcinoma of the bladder underwent serotyping for HLA, A, B, C, and DR antigens. There were 54 men and 16 women patients with a mean age of 65.3 years. Noninvasive lesions (Ta and T1) were present in 50 and 20 were invasive (T2, T3, and T4). Low grade tumors (G1 and G4) were found in 53 and 17 were moderately or poorly differentiated (G3 and G4). Gene frequencies for the HLA determinants in the cancer patients were compared to those for normal English caucasoids. No significant differences were found at either the A, B, C, or DR loci. DR4 was the commonest antigen expressed in bladder cancer patients with an allelic frequency of 39% compared to 28% in the normal population. The presence or absence of the DR4 antigen was not related to the stage or grade of the tumor.

Aged↗
PubMed1983

Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility.

The families of 29 patients with systemic lupus erythematosus and 42 normal subjects were studied to determine the inheritance of the HLA-A, B, C, and DR antigens and also the complement polymorphisms for C2, C4A, C4B, and Bf, which are encoded in the same region of the sixth chromosome. Null (silent) alleles for C4A, C4B, or C2 were found in 24 of the 29 (83%) patients compared with 18 of the 42 (43%) normal controls. HLA-DR3 was present in 20 (69%) of the patients and seven out of 39 (18%) of the normal controls. There was strong linkage disequilibrium between DR3 and the null alleles for C4A and C4B. The data did not permit the relative contributions of DR3 and null factors of C4A and C4B as genetic risk factors to be distinguished. The known association of systemic lupus erythematosus with uncommon inherited and acquired deficiencies of complement components suggests, however, that the presence of null alleles for C4A and C4B, as well as C2, found in most of the patients, is relevant to their genetic susceptibility to this disease.

Adolescent↗