Treatment of hemiplegic migraine with triptans.

The objective of this study was to investigate the efficacy, safety and tolerability of triptans in patients who suffer from familial or sporadic hemiplegic migraine. Seventy-six subjects had used triptans at least once as an abortive treatment. Average triptan response was 6.9 (SD +/-3.1) and adverse event severity 4.9 (SD +/-3.3) on a scale from 0 to 10 (no response or side effect 0, excellent response or unbearable side effects 10). None of the patients had an ischaemic stroke or a heart attack. One patient reported prolonged neurological symptoms, related to a single dose of rizatriptan, but there were no pathological findings in several MRI-scans. Triptans seem to be safe and effective treatment for most hemiplegic migraine patients.

Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura.

Among the few independently replicated genetic associations in migraine are polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and oestrogen receptor (ESR1) genes. We studied the contribution of these genes to migraine susceptibility by genotyping six MTHFR and 26 ESR1 polymorphisms in 898 unrelated migraine with aura (MA) patients and in 900 unrelated healthy controls. There were no differences in the genotype distributions of the previously migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and controls (P-values 0.83 and 0.55, respectively). Thus, we were not able to replicate the previous findings, although our study had considerable power. However, five of the ESR1 SNPs (rs6557170, rs2347867, rs6557171, rs4870062 and rs1801132) that were in strong linkage disequilibrium were nominally associated with MA (uncorrected P-values 0.007-0.034). These results did not, however, remain significant after taking multiple testing into account. Thus it seems unlikely that the studied genes are involved in migraine susceptibility, at least in this sample.

Serum soluble interleukin-2 receptor predicts early remission in patients with recent-onset rheumatoid arthritis treated with a single disease-modifying antirheumatic drug.

OBJECTIVE: To study the value of baseline serum levels of circulating soluble interleukin-2 receptor (sIL-2R) and soluble E-selectin as predictors of early remission in patients with recent-onset rheumatoid arthritis (RA) receiving a single disease-modifying anti-rheumatic drug (DMARD) (SINGLE) or therapy with a combination of DMARDs (COMBI). METHODS: Baseline (n = 157) serum samples originate from the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, in which 195 patients with early and clinically active RA were randomly assigned to receive either SINGLE (initially sulfasalazine) with or without prednisolone, or COMBI therapy (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone). Of the samples, 76 were from SINGLE patients and 81 from COMBI patients. sIL-2R was measured by automated immunoassay analyzer and sE-selectin by enzyme-linked immunosorbent assay. RESULTS: At six months, 7 (9% [95% CI: 4 to 18]) SINGLE and 19 (23% [95% CI: 15 to 34]) COMBI patients were in remission. In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. The area under receiver operating characteristic curve for sIL-2R level was 0.86 (95% CI: 0.62 to 0.95) in SINGLE and 0.57 (95% CI: 0.42 to 0.71) in COMBI (p = 0.006). In SINGLE, the optimal cut offpoint was 442 U/ml, lower levels predicting remission with sensitivity of 83% (95% CI: 73% to 91%) and specificity of 86% (95% CI: 42% to 100%). Likelihood ratio for positive test was 5.9 (95% CI: 1.6 to 32.8). In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. CONCLUSION: Low baseline serum sIL-2R level predicts early remission of patients with active early RA treated with a single DMARD.

Prevalence of Sindbis-related (Pogosta) virus infections in patients with arthritis.

OBJECTIVE: To determine the role of Pogosta virus as a triggering infection in non-specific arthritis. METHODS: Serum samples of 142 patients with acute arthritis were screened for the evidence of Pogosta virus infection. Serological tests for Chlamydia trachomatis, salmonella, parvovirus B19, and Borrelia burgdorferi were also carried out. As verified later, 78 of the patients had rheumatoid arthritis and 63 seronegative poly- or oligoarthritis, while one had systemic lupus erythematosus. RESULTS: In the early stage of the joint symptoms 4 patients with rheumatoid arthritis, 1 with seronegative polyarthritis and 1 with systemic lupus erythematosus had recent Pogosta virus infection. Four of them had probably had Pogosta disease at the time of the onset of arthritis. In 11 patients with a diagnosis of seronegative arthritis, serological evidence of preceding infection due to salmonella or Chlamydia trachomatis was found, strongly suggesting classical reactive arthritis in these cases. CONCLUSIONS: Our study suggests that also a Sindbis virus infection may be associated both to an acute joint inflammation as a part of Pogosta disease or chronic arthritis. At present, this possibility still needs further research.

Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations.

OBJECTIVE: To compare the efficacy of combination therapy with disease-modifying antirheumatic drugs (DMARDs) versus single therapy with DMARDs in the prevention of early cervical spine changes in patients with rheumatoid arthritis (RA). METHODS: One hundred ninety-five patients with recent-onset RA (mean disease duration 8 months) were randomly assigned to receive a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single DMARD with or without prednisolone. After 2 years of followup, cervical spine radiographs were taken of 176 of these patients (85 in the combination-therapy group and 91 in the single-therapy group). These radiographs were evaluated, and the findings were correlated with the therapy strategies as well as with peripheral joint destruction and clinical and laboratory variables describing the disease activity. RESULTS: Anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI; i.e., vertical subluxation), and subaxial subluxation (SAS) were found in only 6 (3.4%), 2 (1.1%), and 5 (2.8%) of the patients, respectively. Interestingly, none of the patients in the combination-therapy group had aAAS or AAI. The incidences of aAAS and AAI in the single-therapy group were 6.6% and 2.2%, respectively. SAS was present in 2 patients (2.2%) in the single-therapy group and in 3 patients (3.5%) in the combination-therapy group. The difference in the incidence of aAAS between the treatment groups was statistically significant (P = 0.029). None of the patients with cervical spine changes achieved remission of RA during the study. CONCLUSION: In the present study, the incidence of cervical spine subluxations in patients treated with single-drug therapy was in accord with findings of previous studies. However, none of the patients in the combination-therapy group had aAAS or AAI. These findings suggest that early, aggressive combination-DMARD therapy with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone can prevent or retard the development of rheumatoid atlantoaxial disorders.

Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locus on 2q.

The genetic contribution to common forms of osteoarthritis (OA) is well established but poorly understood. We performed a genome scan, using 302 markers for loci predisposing to distal interphalangeal joint (DIP) OA. To minimize genetic heterogeneity in our study sample, we identified siblings with a severe, radiologically defined phenotype from the nationwide registers of Finland. In the initial genome scan, linkage analysis in 27 sibships gave a pairwise LOD score (Z) >1.00 with nine of the screening markers. In the second stage, additional markers and family members were genotyped in these chromosomal regions. On 2q12-q13, IL1R1 resulted in Z=2.34 at recombination fraction (theta) 0, allowing a dominant mode of inheritance. Association analysis of markers D2S2264, IL1R1, D2S373, and D2S1789 jointly provided some evidence for a shared haplotype among the affected individuals (P value of.012). Also, multipoint nonparametric linkage analysis yielded a P value of.0001 near the locus IL1R1 and P=.0007 approximately 20 cM telomeric near marker D2S1399, which, in two-point analysis, gave Z=1.48 (straight theta=. 02). This chromosomal region on 2q harbors the interleukin 1 gene cluster and, thus, represents a good candidate region for inflammatory and autoimmune disorders. Three additional chromosomal regions-4q26-q27, 7p15-p21, and Xcen-also provided some evidence for linkage, and further analyses would be justified to clarify their potential involvement in the genetic predisposition to DIP OA.

Somatic serogroups, capsular types, and species of fecal Klebsiella in patients with ankylosing spondylitis.

The purpose of the present study was to find out whether patients with ankylosing spondylitis (AS) carry fecal Klebsiella strains that belong to serotypes or species specific for AS. Somatic serotypes (O groups), capsular (K) serotypes, and biochemically identified species were determined for fecal klebsiellae isolated from 187 AS patients and 195 control patients. The controls were patients with fibromyalgia or rheumatoid arthritis. The 638 isolates of Klebsiella that were obtained represented 161 strains; 81 from AS patients and 80 from the controls. The average number of Klebsiella strains per patient was 1.7 for the AS group and 1.5 for the control group. The most common O group was O1, which was observed for isolates from 23 of 187 AS patients and 24 of 195 control patients. Next in frequency was group O2, which was observed for isolates from 17 AS patients and 15 control patients. Regarding the K serotypes, 59 different types were identified, revealing a heterogeneous representation of Klebsiella strains, without a predominance of any serotype. By biochemical identification, Klebsiella pneumoniae was the most frequently occurring species, being found in 45 AS patients and 45 control patients. Next in the frequency was K. oxytoca, which was observed in 26 AS patients and in 29 control patients. K. planticola and K. terrigena occurred in only a minority of patients. Altogether, when analyzed either separately or simultaneously according to O groups, K serotypes, and biochemically identified species, no evidence of the existence of AS-specific Klebsiella strains was obtained. These findings do not indicate participation of Klebsiella in the etiopathogenesis of AS.

Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.

BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

Periarticular corticosteroid treatment of the sacroiliac joint in patients with seronegative spondylarthropathy.

OBJECTIVE: To evaluate the efficacy of periarticular corticosteroid injection of the sacroiliac joint (SIJ) in patients with seronegative spondylarthropathy in a double blind, controlled study. METHODS: 20 patients with seronegative spondylarthropathy and clinical sacroiliitis entered the study. In 10 patients one affected SIJ was treated with periarticular injection of 1.5 ml (40 mg/ml) methylprednisoloneacetate and 1.5 ml (20 mg/ml) lignocaine (MP group), whereas 10 patients received 1.5 ml isotonic sodium chloride and 1.5 ml (20 mg/ml) lignocaine (non-MP group). Clinical assessment at the onset of the study and after two months follow-up included the patients' estimation of pain in the SIJ by the visual analogue scale (VAS) and by a pain index which was calculated from tenderness and stressing tests on the SIJ. RESULTS: At the two months follow-up examination the VAS (p = 0.02) and the pain index (p = 0.01) had improved significantly in the MP group compared with the non-MP group. CONCLUSION: The results of our study indicate that the periarticular injection of methylprednisolone may be effective in the treatment of clinical sacroiliitis in patients with seronegative spondylarthropathy.

Conversion of patients with rheumatoid arthritis from the conventional to a microemulsion formulation of cyclosporine: a double blind comparison to screen for differences in safety, efficacy, and pharmacokinetics.

OBJECTIVE: To assess whether patients with rheumatoid arthritis (RA) may be converted, on a milligram-to-milligram basis, from conventional cyclosporin A (CyA, Sandimmun) to the microemulsion formulation (Neoral) with maintenance of longterm safety, and to compare cyclosporin A (CyA) pharmacokinetics between formulations. METHODS: In this double blind, multicenter, parallel group study, 51 patients receiving stable conventional CyA maintenance treatment were randomized to continue conventional CyA (n = 27) or to convert to CyA microemulsion (n = 24) and were monitored for 52 weeks. Trough blood CyA levels were measured before and at intervals after conversion. CyA steady-state area under the curve was assessed one week before and 2 and 6 weeks after randomization in 15 patients in each treatment arm. CyA trough levels and pharmacokinetic results remained unknown to investigators throughout the study. CyA doses were titrated as necessary on the basis of clinical evaluation and disease activity assessments. RESULTS: Initial mean daily doses were 3.5 mg/kg/day (conventional CyA) and 3.3 mg/kg/day (CyA microemulsion) and did not change significantly during the study. The mean bioavailability of CyA from the microemulsion formulation was 23% higher than from conventional CyA. Replicate assessments indicated a more reproducible pharmacokinetic profile with CyA microemulsion. The overall incidence and nature of adverse events and changes in vital signs and laboratory variables were similar in both groups. No clinically relevant differences in efficacy were found between treatments. No loss of efficacy and no tolerability problems occurred after conversion from conventional to microemulsion CyA. CONCLUSION: Existing CyA dosing guidelines, formulated for conventional CyA, are suitable for longterm CyA microemulsion therapy of patients with RA. These results indicate the pharmacokinetic advantages of the microemulsion formulation.

IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis.

OBJECTIVE: To investigate the possible predominance of certain Klebsiella pneumoniae capsular types in the pathogenesis of ankylosing spondylitis (AS). METHODS: The prevalence of IgA class antibodies against three different K. pneumoniae strains (with capsular types 21, 30 and 43) was studied in the sera of 177 patients with AS and of 100 healthy blood donors using an enzyme-linked immunosorbent assay. RESULTS: The median Klebsiella-specific antibody levels were always higher in patients than in controls regardless of the serotype used as antigen. When the prevalence of increased antibody levels was compared between the groups, it was highest against the strain with capsular type 30, whereas against strains 21 and 43 it was similar among patients and controls. CONCLUSIONS: A broad range of Klebsiella serotypes may be involved in the pathogenesis of AS. Thus, it is important to take the different Klebsiella serotypes into particular account in these studies.

Efficacy and safety of meloxicam in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and safety of meloxicam, a new acidic enolic nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in patients with rheumatoid arthritis (RA). METHODS: Meloxicam 15 and 7.5 mg daily was administered for 21 days in this double blind, randomized, placebo controlled study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and 147 received placebo. RESULTS: Meloxicam 15 mg once daily was significantly superior (p < 0.05) to placebo in 3 of the 4 primary endpoints (disease activity assessed by the investigator, disease activity assessed by the patient, and reduction of the number of tender/painful joints). No difference was observed regarding number of swollen joints. The difference between meloxicam 7.5 mg once daily and placebo reached statistical significance in 2 of the 4 primary endpoints, disease activity assessed by the patient and number of tender/painful joints. A statistically significant difference between meloxicam 1.5 mg and 7.5 mg was not observed for any primary endpoint. The rating of global tolerance by investigators and patients at the end of the study was similar in the 3 treatment groups, indicating that meloxicam and placebo were generally similarly well tolerated. However, there was a slightly higher incidence of gastrointestinal (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5 mg, and meloxicam 15 mg groups, respectively. None were serious. CONCLUSION: Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and symptoms of RA.

IgA1 and IgA2 subclass antibodies against Klebsiella pneumoniae in the sera of patients with peripheral and axial types of ankylosing spondylitis.

OBJECTIVE: To study further the Klebsiella specific serum antibody response in patients with axial and peripheral types of ankylosing spondylitis (AS). METHODS: IgA1 and IgA2 subclass antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay in the sera of 171 patients with axial or peripheral type AS, and in sera of 100 healthy controls. The effect of 26 weeks of sulphasalazine treatment on the antibody levels in the two types of AS was also analysed. RESULTS: K pneumoniae specific antibody levels of both IgA1 and IgA2 subclasses were increased in the sera of patients with AS compared with healthy controls. The increased levels were present in patients with axial and with peripheral AS, and there were no statistically significant differences in the antibody levels between these two groups. Sulphasalazine treatment decreased the Klebsiella specific antibody level of IgA1 subclass in patients with axial AS, but there were no statistically significant changes in the IgA2 subclass, or in the patients with peripheral type AS. CONCLUSIONS: These results agree with earlier published findings suggesting that IgA (especially Klebsiella specific IgA) may have a role in the pathogenetic mechanisms of both peripheral and axial types of AS. In addition, it seems that both IgA1 and IgA2 subclasses are involved in the disease process.

Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of patients with axial and peripheral form of ankylosing spondylitis.

IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in two separate patient populations of 99 and 85 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the presence or absence of peripheral arthritis. The patients with peripheral type AS had increased levels of IgM and IgA class antibodies against K. pneumoniae, whereas the patients with axial type AS had increased levels of IgG and IgA class antibodies to K. pneumoniae, as well as IgA class antibodies against E. coli and P. mirabilis bacteria. Sulphasalazine treatment decreased the IgM and IgA class antibodies in peripheral AS and IgA class antibodies in axial AS against K. pneumoniae LPS. The antibody levels were also decreased against E. coli and P. mirabilis bacteria in the sera of patients with axial AS. The immunological findings in patients with peripheral and axial form of AS were different from each other and thus may reflect different aetiopathogenetic mechanisms for these two types of AS.

Evaluation of Epilepsy Expert--a decision support system.

Epilepsy Expert is a decision support system based on the International Classification of Epilepsies and Epileptic Syndromes (1989). The aim of this study was to evaluate the Epilepsy Expert. First the diagnostic performance was validated. This was done in 3 stages: collection of the patient cases, determination of the 'correct diagnoses' and testing the system. How the users perceived the functionality of the system was studied by using an inquiry. Three physicians, experts of epilepsy, from different hospitals were asked to choose 10 patients. In the patient description was a short history, a detailed description of the seizure, EEG findings and their own diagnosis. Next, each expert made a diagnosis of the cases supplied by other experts by using the International Classification of Epilepsies and Epileptic Syndromes. The 'correct diagnosis' (so-called majority agreement) was the diagnosis given by the majority of the experts. The diagnosis of each expert was compared with the 'correct diagnosis'. The diagnoses obtained by the Epilepsy Expert were then compared with the 'correct diagnoses'. In the evaluation the expert physicians agreed on 37% of cases and all 3 disagreed on 17%. A majority agreed on 25 cases, which were used in the evaluation. In these 25 cases the experts' (A,B,C) diagnoses were correct or partly correct in 100, 64, 80% of cases, respectively. The program's diagnoses were correct or partly correct in 80% (module I) and 76% (modules IV and V) of cases. In the evaluation Epilepsy Expert was found to be only partly successful. The main reason for this was the weakness of the international classification. However, the program seems to be very close to the level of the experts. According to this limited inquiry Epilepsy Expert is not suitable for clinical use, because it is, for example, too simple and does not contain enough information.

IgM, IgA and IgG class serum antibodies against Klebsiella pneumoniae and Escherichia coli lipopolysaccharides in patients with ankylosing spondylitis.

Igm, IgA and IgG class serum antibodies against Klebsiella pneumoniae and Escherichia coli lipopolysaccharides (LPS) were studied by ELISA in two separate AS patient populations of 99 and 81 subjects and in 102 healthy blood donors. In the first patient population increased levels of IgM and IgG class antibodies against K. pneumoniae LPS were observed in patients with active AS. In the population with active AS, increased levels of IgM, IgA and IgG class antibodies against K. pneumoniae LPS and IgA class antibodies against E. coli LPS were observed. Sulphasalazine treatment decreased IgM and IgA class antibody levels significantly against K. pneumoniae LPS and IgM class antibodies against E. coli LPS. These findings suggest that a significant part of the anti-Klebsiella antibodies found in AS patients is directed against the LPS component of Klebsiella.

Antibodies to Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in ankylosing spondylitis: effect of sulfasalazine treatment.

OBJECTIVE: To make a longitudinal study of antibodies to Klebsiella pneumoniae in patients with ankylosing spondylitis (AS) and to assess treatment effects. As a comparison we measured antibodies of 2 other gut associated bacteria, Escherichia coli and Proteus mirabilis. METHODS: In a double blind study in 84 Finnish outpatients with AS before and after 26 weeks' treatment with sulfasalazine or placebo we measured serum antibodies to Klebsiella pneumoniae, E. coli and Proteus mirabilis with ELISA: Serum samples of 100 healthy blood donors served as controls. RESULTS: The levels of IgA class antibodies to all 3 bacteria were statistically significantly higher in the sera of the patients compared to the controls. During sulfasalazine treatment significant decreases were observed in concentrations of the IgA class antibodies to Klebsiella and E. coli whereas only a slight decrease was observed in the concentrations of IgA antibodies to Proteus mirabilis. There were no correlations between the clinical and laboratory results observed with sulfasalazine and decrease in concentrations of IgA class antibodies. CONCLUSION: Our results agree with the role of gut associated lymphoid tissue in the pathogenesis of AS, but do not totally exclude Klebsiella pneumoniae as a specific agent contributing to the development of AS.

Multiallelic polymorphism of the cartilage collagen gene: no association with osteoarthrosis.

OBJECTIVES: To determine whether any of the type II collagen alleles are associated with generalised osteoarthrosis or osteoarthrosis of the finger joints in the genetically isolated Finnish population. METHODS: Two patient cohorts with evidence for only primary osteoarthrosis and a cohort of healthy control subjects were selected from the Helsinki University Central Hospital and the Rheumatism Foundation Hospital in Finland. Forty one patients with primary generalised osteoarthrosis, 49 patients with osteoarthrosis of the finger joints, and 48 control subjects were included. Two markers of the type II collagen gene, a PvuII polymorphism and a VNTR polymorphism, were analysed from each subject. RESULTS: Four different alleles of the VNTR marker were observed and the relative risks associated with the different VNTR alleles varied between 0.39 and 1.24 among the patients with generalised osteoarthrosis and between 0.67 and 2.33 among the patients with osteoarthrosis of the finger joints. The PvuII polymorphism detected two different alleles and the associated relative risks were 0.82 and 1.82 for the patients with generalised osteoarthrosis, and 1.04 and 0.96 for the patients with osteoarthrosis of the finger joints. CONCLUSIONS: A major predisposing allele of the type II collagen gene as the causative factor for osteoarthrosis could be excluded in this population. A spectrum of mutations associated with different alleles of this gene could not be excluded, however. Further, these two forms of cartilage disease can be caused by gene defects with reduced penetrance and the effect of such an allele is easily masked under the high frequency of normal alleles.

Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix.

Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.