Biomedical subjects

M J Rowley

Publications and source records attributed to M J Rowley.

At least 55 records · Page 3Linked to original sources

PubMed1997

High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect a hyperimmune state that precedes the onset of insulin-dependent diabetes.

Pancreatic islet beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is an autoimmune T cell-mediated process. Peripheral blood T cells, which proliferate to islet antigens such as glutamic acid decarboxylase (GAD), (pro)insulin or tyrosine phosphatase IA-2, can be detected in at-risk, first degree relatives of people with IDDM. However, cross-sectional studies cannot define the relationship between T cell responses and progression to IDDM. Longitudinal studies were therefore undertaken on 50 at-risk, first degree relatives tested at least yearly for up to 4 years, during which time five developed IDDM. Peripheral blood T cell responses to a GAD67(aa208-404)-glutathione-S-transferase (GST) fusion protein, GST, insulin and tetanus toxoid were measured, together with antibodies to islet cells, GAD, insulin and IA-2. High levels of antibodies to GAD or insulin were generally associated with low T cell responses to these antigens. Relatives who developed IDDM were characterized by high levels of antibodies to insulin and/or islet cells, and high T cell responses to GAD67-GST and tetanus, but not insulin, in the 24 months before clinical diagnosis. Cross-sectionally, T cell responses to GAD67(aa208-404)-GST and to full-length GAD65-GST were highly correlated (r=0.75, P<0.002). In conclusion, increased cellular immunity to the mid region of GAD67 was a marker of late pre-clinical IDDM, but appears to reflect a more general, transient state of cellular immune hyperresponsiveness.

Adolescent↗

PubMed1997

Evaluation of ICA512As in combination with other islet cell autoantibodies at the onset of IDDM.

OBJECTIVE: The ICA512 pancreatic islet autoantigen is a putative tyrosine phosphatase that is co-identified with the earlier described 40-kDa autoantigen. We report the frequency of autoantibodies to islet cell antigen 512 (ICA512As) in recent-onset IDDM and compare this with other islet cell autoantibodies, including those to GAD (GADAs), insulin (IAAs), and islet cell cytoplasm (ICAs) identified by immunofluorescence. RESEARCH DESIGN AND METHODS: Sera from 232 children aged between 9 months and 14.9 years collected within 14 days of diagnosis were tested for ICA512As by a radioimmunoprecipitation assay. The results were compared with previously reported data for GADAs (n = 232), IAAs (n = 167), and ICAs (n = 230). RESULTS: The frequency of a positive result for ICA512As in children with newly diagnosed IDDM was 60%. The frequency was greater for children with an age of onset between 5 and 10 years (69%) than for children aged < 5 years (49%) and aged between 10 and 15 years (56%). The frequencies for other autoantibody reactivities were 69% for GADAs, 65% for IAAs, and 70% for ICAs. A combination of positive results for ICA512As, GADAs, and IAAs gave a sensitivity for the diagnosis of childhood IDDM of 95%, which was not significantly increased by a positive result for ICAs (96%). CONCLUSIONS: Our results further establish that positivity in a combination of tests is more valuable for the prediction of IDDM than a result for any single autoantibody and that the age of the patient should be considered when selecting the combination of tests to use.

Adolescent↗

PubMed1997

The effect of HLA-DRB1 disease susceptibility markers on the expression of RA.

The study was designed to examine the effect on clinical expression of rheumatoid arthritis (RA) of HLA alleles, particularly DR4 and DR1 that contain susceptibility sequences for RA in the third hypervariable region (HVR3) of HLA-DRB1. We studied 114 consecutive Australian patients with RA attending a hospital outpatient clinic. The effects on indices of disease severity and activity of HLA DR4 and DR1, the DRB1*04 subtypes, and the polymorphism in the RA susceptibility sequence (QRRAA or QKRAA) were examined. The patients were initially divided into 6 groups, DR4,4; DR4,1; DR1,1; DR4/X; DR1,X, and DRX/X, and then further subdivided according to the actual HVR3 susceptibility sequence. The high risk conferred by the HVR3 susceptibility sequence, present in 76%, was confirmed, but 24% of the patients with long-standing seropositive erosive RA lacked this sequence. Among these those with DR2 had early-onset severe disease, and those with DR3 had late-onset milder disease. Differences in expression correlated with polymorphisms in the susceptibility sequence, in that active RA was associated more with QRRAA than QKRAA. There was no correlation of any HLA allele with disease severity. Our finding that the presence of the HVR3 sequence confers susceptibility and also influences the clinical expression and tempo of progression of RA suggests a role in pathogenesis for antigen presentation, whether of an autoantigenic molecule or a persisting infection.

Adult↗

PubMed1997

IgG subclasses of antibodies to type II collagen in rheumatoid arthritis differ from those in systemic lupus erythematosus and other connective tissue diseases.

OBJECTIVE: To compare IgG subclass distribution of autoantibodies to native type II collagen in patients with rheumatoid arthritis (RA) and in other rheumatic and inflammatory diseases including systemic lupus erythematosus (SLE). METHODS: The IgG subclass of antibodies to native type II collagen were measured by modified ELISA using chemiluminescent detection and subclass-specific monoclonal antibodies in sera that contained IgG antibodies to collagen using conventional ELISA. RESULTS: Antibodies to native type II collagen were present in sera of 20% of 323 patients with RA. 9% of 211 patients with SLE, 12% of 50 patients with osteoarthritis, and 13% of 75 patients with other chronic inflammatory diseases, but the highest levels occurred in patients with RA. The IgG subclass distribution of these antibodies differed markedly according to disease. In RA the predominant subclasses were IgG1 (58%) and IgG3 (47%), whereas in SLE the predominant subclass was IgG4 (69%). IgG2 was represented across all disease groups. Overall the frequency of IgG1 and/or IgG3 antibodies to type II collagen (84%) was significantly greater in RA than in other disease groups combined (20%) (p < 0.0001). CONCLUSION: Antibodies to native collagen in RA were predominantly of the complement fixing and potentially damaging subclasses IgG1 and IgG3, but in SLE were of the non-complement fixing subclass IgG4; in other diseases, where present, antibodies were mostly IgG2 and of low level. These observations support the importance of autoimmunity to collagen in the pathogenesis of RA.

Arthritis, Rheumatoid↗

PubMed1996

Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression.

OBJECTIVE: To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. METHODS: Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. RESULTS: IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. CONCLUSION: Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA.

Adult↗

PubMed1996

Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases.

OBJECTIVE: To investigate the occurrence of IgG antibodies to aggrecan in synovial fluids (SF) from patients with arthritis and various articular diseases, and to determine the nature of epitopes present within aggrecan that react with these antibodies. METHODS: SF samples were reacted with native aggrecan, reduced and alkylated aggrecan, chondroitin sulfate, and keratan sulfate, using dot-blots and a novel enzyme-linked immunosorbent assay (ELISA). The nature of the epitopes present on aggrecan was elucidated using Western blots and a competitive inhibition ELISA. RESULTS: IgG antibodies to aggrecan were found in > 50% of the SF samples tested. No IgG antibody reactivity was observed in serum from the same patients. The antibodies appeared to react predominantly with native aggrecan, and there was no disease specificity. It was shown that the epitopes to these antibodies were located within the N-terminal region of the core protein. CONCLUSION: This study demonstrates the frequent occurrence of IgG antibodies to aggrecan in human SF. The major epitope is located in the G1 domain of the aggrecan core protein. These IgG antibodies appear to be produced locally within the synovial cavity, probably in response to various articular diseases, resulting in the loss of native aggrecan from articular cartilage.

Adult↗

PubMed1996

Lack of autoimmune serological reactions in rodent models of insulin dependent diabetes mellitus.

Spontaneous insulitis with insulin-dependent diabetes mellitus (IDDM) in rodent models, the BB rat and NOD mouse, has clarified the pathogenesis of and guided decisions on interventional therapy for human IDDM. However, the occurrence in such models of a standard marker of human IDDM, autoantibodies to beta islet cell constituents, has been controversial. Hence we assessed diabetes-prone rodents for the frequencies of raised levels of auto-antibodies to glutamic acid decarboxylase GAD (anti-GAD), insulin and heat shock protein 65 (HSP-65) in relation to levels in non-diabetes-prone animals and levels in human diabetic sera. Assays were performed sequentially at various ages of life. The immunoassays used for anti-GAD and anti-insulin were those validated for sensitivity and specificity for detection of the corresponding autoantibodies in human IDDM sera at international workshops. Positive controls included human IDDM sera with reactivity with GAD or insulin and, for mouse anti-GAD, the highly reactive monoclonal antibody, GAD-6. The results were that levels of autoantibodies in diabetes-prone BB rats or NOD mice to the "IDDM-relevant' autoantigens in our panel did not exceed levels in control rats or mice, and were much lower than levels in humans with IDDM. We conclude that the BB rat and NOD mouse represent a model, but not a facsimile, of human IDDM and that therapeutic successes in such models should be interpreted with caution in relation to interventional therapy for human IDDM.

Animals↗

PubMed1996

Comparative epitope mapping of antibodies to collagen in women with silicone breast implants, systemic lupus erythematosus and rheumatoid arthritis.

Previous work has shown that women with silicone gel breast implants have an increased frequency of autoantibodies to collagen types I and II. 70 women without a specific autoimmune disease, using criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were also studied. There was a high frequency of autoantibodies to collagen in each of the groups when compared to the healthy controls. The specificities of these antibodies were found to differ markedly when examined by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Sera from women with silicone implants reacted with multiple peptides of type I collagen in an individual-specific manner, but sera from women with SLE or RA reacted weakly with a restricted range of peptides. Against type II collagen, sera from women with RA reacted strongly with multiple peptides, while sera from women with silicone implants or SLE reacted only weakly or not at all. The patterns of reactivity against collagens by sera from women with silicone implants suggest that silicone can act as an adjuvant to enhance the immunogenicity of type I collagen.

Adult↗

PubMed1996

Immunoreactivity of antimitochondrial autoantibodies in Japanese patients with primary biliary cirrhosis.

The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using procine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1996

Pancreatic beta cell function and antibodies to glutamic acid decarboxylase (anti-GAD) in Chinese patients with clinical diagnosis of insulin-dependent diabetes mellitus.

Antibodies to glutamic acid decarboxylase (anti-GAD) and pancreatic beta cell secretory function were measured in 39 consecutive Chinese patients with a clinical diagnosis of insulin-dependent diabetes mellitus (IDDM) (19 males, mean +/- SD age. 37 +/- 15 years; body mass index (BMI), 22 +/- 4 kg/m2; mean duration of disease, 6.7 +/- 5.6 years). IDDM was defined on the basis of acute symptoms with heavy ketonuria (> 3+) or ketoacidosis at diagnosis, or requirement for continuous insulin treatment within one year of diagnosis. Insulin deficiency was defined as a post-glucagon stimulated plasma C-peptide concentration < or = 0.6 nmol/l. Overall, anti-GAD antibodies were positive (> 18 units) in 23% (n = 9) of these patients. Of the 39 patients, 29 (74%) were insulin deficient and 10 (26%) were non-insulin deficient. Anti-GAD antibodies were positive in 31% of the insulin-deficient patients but in none of the non-insulin-deficient group. Insulin deficiency and anti-GAD positivity were associated with younger age, earlier age of clinical onset and lower BMI. There were independent negative relationships between levels of anti-GAD antibodies and blood pressure and a positive relationship between insulin dosage and albuminuria. This study emphasises the difficulty in differentiating clinically between IDDM and NIDDM in Chinese patients. Despite the acute presentation, these patients had variable pancreatic beta cell secretory function. The varying duration of disease may partly explain the low prevalence of positive anti-GAD antibodies in these patients, but seems unlikely to explain fully the difference from Caucasian IDDM patients.

Adult↗

PubMed1996

Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly diagnosed adult-onset diabetes mellitus.

This study aimed to determine the prevalence of antibodies against glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to beta-cell function in adults newly-diagnosed with diabetes mellitus. beta-cell function was assessed in adults aged 25-70 years newly-diagnosed with diabetes mellitus (n = 84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. beta-cell function was evaluated by the true insulin (defined as immunoreactive insulin minus proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true insulin curve (normal 16830-107700 pmol min/I) and the sum of the 30 and 60 min incremental response (normal 285-3295 pmol/I). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were insulin deficient showing little or no true insulin release. Of the insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without insulin deficiency (P < 0.001). Seven (58%) insulin deficient subjects were ICA positive, whereas only two (3%) non-insulin deficient subjects were ICA positive (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not insulin deficient (P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both antibodies for detecting insulin deficiency was 50%. The specificity for detecting insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus as a new diagnosis are insulin deficient using our criteria. Loss of beta-cell function in two thirds of individuals who are insulin deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of beta-cell damage creates the potential for immune modulation to limit such damage.

Adult↗

PubMed1996

Low prevalence of immunogenetic markers of IDDM in adult Koreans with diabetes detected on OGTT.

In the Asian populations, it is not uncommon for adult patients with NIDDM to eventually lose beta-cell function and develop IDDM. Accepting that IDDM is an autoimmune disease, which occurs on a genetic background, it could by hypothesized that by measuring autoantibody prevalence and HLA DQ gene polymorphism, known important prediagnostic markers of IDDM, the prevalence of adult-onset IDDM in patients with previously undiagnosed NIDDM patients could be estimated. To do this, anti-GAD prevalence and HLA DQ A1 and DQ B1 polymorphisms after PCR amplification of genomic DNA were analyzed in 121 newly diagnosed diabetic patients of Yonchon cohort and compared to the results with those of 100 matched health control subjects. We also compared the results with those of other populations to assess the difference of genotype distribution. The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 controls had positive antibodies. Among those who were positive, their titer of antibodies to GAD were not high. No statistically significant differences in the distribution of either mean levels of anti-GAD or DQA1 and DQB1 alleles were found comparing NIDDM patients to controls. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the Korean adult control population was similar to that of US Caucasians (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles among recent-onset NIDDM patients, not different compared to controls suggests that diabetes in Korean adults is unlikely to have an autoimmune component to its pathogenesis.

Adult↗

PubMed1996

Immunosusceptibility genes in rheumatoid arthritis.

The polygenic predisposition to RA is conferred particularly by disease susceptibility sequences in the HVR3 of HLA DRB1 present in those subtypes of DR4 and DR1 that are associated with RA. The aim of this study was to examine predisposing interactions between genes encoding HLA and immunoglobulin molecules. Accordingly, we compared the genetic background of 114 Australian patients with RA with that of Australian controls of similar ethnic background. We identified HLA-A, B, and DR phenotypes serologically, HLA-DR, DQ alleles, and subtypes of DR4 by DNA typing, and Gm allogenotypes and immunoglobulin switch region polymorphisms by RFLP. For the subjects with RA, we confirmed previously reported observations that included an excess of females, 71%, a high frequency of HLA types DR4 or DR1 of 77% versus controls 47%, and a high frequency of the HVR3 susceptibility sequences of 76%, with 24% homozygous, and 52% heterozygous for the sequences. We observed other genetic correlations in RA that included increases in frequencies of DR4 in males, DR1 in females, the class I specificity HLA-B27 overall but more particularly in females, 24% in females, versus 5% of controls, HLA-DQB1*0302 (DQ8) in DR4*0401-positive patients, and the Gm allogenotype 1,2,3;23 +/- ; 5,10, 15% of patients versus 4% of controls. Examination of switch region genes gave no evidence of differences in the polymorphisms distributions. Thus, the major genetic risks for RA that are conferred by female gender and the HVR3 of HLA DRB1 are modulated by interactions between gender and HLA class I and class II alleles, and the Gm allogenotype.

Adult↗

PubMed1996

Diabetic sera react with the glutamic acid decarboxylase molecule in a dimeric-oligomeric form.

Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). This was initially identified as a 64-65 kD molecule according to migration in gels after immunoprecipitation from pancreatic islets. We studied the antigenicity of two different radiolabelled preparations of GAD, derived either by affinity purification from porcine brain and known to contain GAD 65 and GAD 67, or by expression from a cDNA for human GAD 65 by rabbit reticulocyte lysate (RRL). Radiolabelled immunoprecipitated pellets from the reaction of potent antisera to GAD from patients with IDDM were examined by autoradiography after SDS-PAGE under reducing or non-reducing conditions. Also, preparations of porcine brain GAD were "depleted' of GAD by exposure to antisera, and then similarly re-examined. Autoradiography of radiolabelled GAD either affinity purified from porcine brain, or expressed by RRL, showed that the immunoprecipitated protein migrated under non-reducing conditions according to a M(r) of approximately 110-130 kD, corresponding to dimeric forms of monomeric GAD of approximately 55-65 kD. Depletion by immunoprecipitation of this minor higher M(r) component from preparations of GAD left, in the supernatant, an abundance of GAD of M(r) 64-65 kD corresponding to monomer that was completely non-reactive with potent IDDM sera. We conclude that IDDM sera react with the GAD molecule in a dimeric (or oligomeric) form. Our findings have general connotations for self-tolerance and autoimmunity.

Animals↗

PubMed1996

Autoantibodies to M2 mitochondrial autoantigens in normal human sera by immunofluorescence and novel assays.

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (anti-M2), directed against the E2 subunits of the 2-oxo-acid dehydrogenase complexes (2-OADC), chiefly pyruvate dehydrogenase complex (PDC-E2). We present here a detailed study, based on a large panel of normal sera, of the specificity of tests for anti-M2 by immunofluorescence and for anti-PDC by other assays for the diagnosis of PBC. The assays for anti-PDC included immunoblotting with bovine heart mitochondria, ELISA using recombinant PDC-E2 and an enzyme inhibition assay using purified porcine PDC. The positivity rates for normal sera were 0 (0/170), 2 (4/201), 1.5 (3/198) and 0% (0/186) for immunofluorescence, immunoblotting, ELISA and the enzyme inhibition assay, respectively. The seven positive reactions detected either by immunoblotting (n = 4) or ELISA (n = 3) were negative by the other three assays and in no instance did biochemical indices give any indication of chronic liver disease. Thus, as judged by reactivity with normal sera, the specificity of a positive test for the antibody to the major M2 autoantigen (PDC-E2) is 100% for immunofluorescence and the enzyme inhibition assay, 98% for immunoblotting and 98.5% for ELISA.

Autoantibodies↗

PubMed1995

Continuity of care by a midwife team versus routine care during pregnancy and birth: a randomised trial.

OBJECTIVE: To compare continuity of care from a midwife team with routine care from a variety of doctors and midwives. DESIGN: A stratified, randomised controlled trial. PARTICIPANTS AND SETTING: 814 women attending the antenatal clinic of a tertiary referral, university hospital. INTERVENTION: Women were randomly allocated to team care from a team of six midwives, or routine care from a variety of doctors and midwives. MAIN OUTCOME MEASURES: Antenatal, intrapartum and neonatal events; maternal satisfaction; and cost of treatment. RESULTS: 405 women were randomly allocated to team care and 409 to routine care; they delivered 385 and 386 babies, respectively. Team care women were more likely to attend antenatal classes (OR, 1.73; 95% CI, 1.23-2.42); less likely to use pethidine during labour (OR, 0.32; 95% CI, 0.22-0.46); and more likely to labour and deliver without intervention (OR, 1.73; 95% CI, 1.28-2.34). Babies of team care mothers received less neonatal resuscitation (OR, 0.59; 95% CI, 0.41-0.86), although there was no difference in Apgar scores at five minutes (OR, 0.86; 95% CI, 0.29-2.57). The stillbirth and neonatal death rate was the same for both groups of mothers with a singleton pregnancy (three deaths), but there were three deaths (birthweights of 600 g, 660 g, 1340 g) in twin pregnancies in the group receiving team care. Team care was rated better than routine care for all measures of maternal satisfaction. Team care meant a cost reduction of 4.5%. CONCLUSION: Continuity of care provided by a small team of midwives resulted in a more satisfying birth experience at less cost than routine care and fewer adverse maternal and neonatal outcomes. Although a much larger study would be required to provide adequate power to detect rare outcomes, our study found that continuity of care by a midwife team was as safe as routine care.

Adult↗

PubMed1995

Differing frequency of autoantibodies to glutamic acid decarboxylase among Koreans, Thais, and Australians with diabetes mellitus.

The wide racial-geographic differences in the incidence and prevalence of insulin-dependent diabetes mellitus (IDDM) between Europids and Asian populations prompted us to compare frequencies of positivity of autoantibody to glutamic acid decarboxylase (GAD). The patients with IDDM included 41 Koreans, 30 Thais, and 45 Australian Europids; the Koreans included 14 cases regarded as atypical IDDM by reason of a delayed requirement for insulin treatment. Autoantibodies were measured by radioimmunoprecipitation using iodinated purified porcine brain GAD. The frequency of positive tests for anti-GAD of 30% (8/27) for Koreans and 51% (20/39) for Thais was significantly lower than the 84% (38/45) for Australian Europids, even after stratifying by age of onset. Correspondingly, the mean levels of anti-GAD among seropositive cases were significantly lower for Koreans than for Australian Europids. In contrast to Thais and Australians, more than half the Koreans were diagnosed at age > 20 years, but there was no significant difference in positivity for anti-GAD between those over or under the age of 20 at diagnosis. The different frequency of positivity in tests for anti-GAD among Koreans, Thais, and Australian Europids with IDDM suggests that there is a greater etiologic heterogeneity of IDDM among Asian than Europid populations, in whom autoimmune destruction of pancreatic islets predominates.

Adolescent↗

PubMed1995

Antibody reactivity to mycobacterial 65 kDa heat shock protein: relevance to autoimmunity.

Reactivity to the mycobacterial 65 kDa heat shock protein (HSP 65) has been implicated in the pathogenesis of adjuvant arthritis in the rat, and may be involved in the pathogenesis of rheumatoid arthritis or other autoimmune diseases in humans. Accordingly this study sought quantitative or qualitative differences in the antibody reactivity to HSP 65 between normal controls, patients with the multisystem autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and patients with the mycobacterial infections, tuberculosis (TB) and leprosy. Levels of antibodies to recombinant HSP 65 in serum were measured by ELISA in normal subjects and in patients with RA, SLE, TB or leprosy. Antibody reactivity was examined by Western blotting using polypeptide fragments of HSP 65 derived by recombinant DNA techniques, or by digestion with trypsin or cyanogen bromide (CNBr). Reactivity to a synthetic peptide, the adjuvant arthritis T-cell epitope of HSP 65 (180-188), was tested by ELISA. High levels of antibodies to full length recombinant HSP 65 from Mycobacterium bovis were present in all the groups tested. By Western blot analysis, most reactivity with intact HSP 65 was retained in a 32 kDa tryptic fragment, judged by sequencing and size estimations to represent amino acid residues 118- approximately 388. This sequence included a major T-cell epitope for adjuvant arthritis (180-188), but these nine amino acids were not essential for B-cell reactivity since most sera also reacted with residues 188-540 which lack the T-cell epitope. Moreover, the 180-188 synthetic peptide was unreactive by ELISA, and did not inhibit reactivity with the intact recombinant HSP 65. In conclusion, most individuals had antibodies to mycobacterial HSP 65, presumably resulting from previous bacterial infections. The magnitude of the response was unrelated to the occurrence of systemic autoimmune disease, and the pattern of antibody reactivity with recombinant and proteolytic fragments of HSP 65 suggests that the major B-cell epitope is conformational and consists of discontinuous regions of the molecule.

Amino Acid Sequence↗