Long-term outcome of anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis.

OBJECTIVES: A significant proportion of patients with juvenile spondyloarthritis (JSpA) are refractory to treatment with established medications. The objective of this study was to assess long-term efficacy of treatment with anti-TNF agents in patients with JSpA. METHODS: An observational study of 16 patients with JSpA from 3 centres treated with infliximab (n=10) and etanercept (n=6) was performed, with a median follow-up period of 7.2 years. Prospective data was collected according to a standardized protocol. Outcomes examined were TEC, TAJC, markers of inflammation (ESR, CRP), functional assessments (C-HAQ, BASDAI, BASFI), and ongoing requirement for anti-TNF treatment. RESULTS: 13/16 patients (83%) had achieved clinical remission 6 months into the treatment. Improvement was sustained over time, with a median TAJC and TEC of 0 at any time point after 6 weeks. 6/16 patients (38%) showed a flare of arthritis after a median of 3.5 years. Two patients with hip disease prior to treatment required an arthroplasty 3 and 8 years post anti-TNF initiation. Patients showed progression of sacroiliitis with median modified New York score of 1 (range 0-3) at time of diagnosis and 3 (range 0-4) at last follow-up (p=0.002). Median BASDAI at last follow up was 1.6, median BASFI 3.1. Two patients developed transient reactions (one generalised, one local); no patient developed other adverse effects during the study. CONCLUSIONS: Anti-TNF treatment in JSpA refractory to standard treatment results in good long-term disease control except for pre-existing hip disease. However, radiographic evidence suggests inferior efficacy for control of sacroiliac joint disease.

A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodies at the synovial level in patients with rheumatoid arthritis.

BACKGROUND: Several studies have confirmed that galectin-1 (Gal-1) plays a role in controlling the immune response because of its pro-apoptotic effect. Although studies based on a rheumatoid arthritis (RA) mouse model have suggested a crucial role for Gal-1 in inflammation, clinical data are lacking. We have detected the presence of autoantibodies against galectins in blood, but their physiological meaning remains unknown. OBJECTIVES: To compare plasma and synovial levels of Gal-1 in RA patients and in healthy controls, and correlate them with clinical parameters. METHODS: Plasma and synovial (non-arthritic knee effusion) samples were collected from RA patients and healthy donors. All patients were receiving treatment with steroids and/or disease-modifying anti-rheumatic drugs (DMARDs). A blood sample was taken at a baseline visit to determine plasma anti-cyclic citrullinated peptide (anti-CCP) antibodies, tumour necrosis factor alpha (TNF-α), Gal-1, and anti-Gal-1 autoantibodies. RESULTS: Although plasma levels of Gal-1 were similar in patients and controls, the concentration of Gal-1 was significantly reduced in the synovial fluid of patients with RA. This reduction was not correlated with TNF-α or C-reactive protein (CRP) levels. However, the decrease in synovial Gal-1 correlated with a significant increase in anti-Gal-1 autoantibodies and anti-CCP antibody titres, suggesting a physiological effect of autoantibodies limiting the amount Gal-1 and potentially blocking its biological effect in RA patients. CONCLUSION: Gal-1 levels were significant reduced at the synovial level in RA patients, possibly as a consequence of the increase in anti-Gal-1 autoantibodies.

2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis.

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.

The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis. METHODS: In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (∼10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper. RESULTS: A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference -3.5 [95% CI -15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period). CONCLUSION: Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment.

Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's assessment of arthritis pain (pain), patient's assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded. RESULTS: At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

Prevalence of community-acquired and nosocomial infections in hospitalized patients with systemic lupus erythematosus.

Infections are an important cause of morbidity and mortality in systemic lupus erythematosus. We aimed to determine the incidence and characteristics of infections in patients hospitalized because of systemic lupus erythematosus, and to identify which factors influence their outcome. The medical records of patients with systemic lupus erythematosus hospitalized between January 2002 and December 2007 were reviewed according to a standardized case form including demographic, clinical, and therapeutic data. The diagnosis of infection was based on clinical findings, the identification of the causative agent or response to antibiotic treatment. The study included 473 patients (mean age 30 +/- 11 years; 421 (89%) female) who were hospitalized for a mean of 13 +/- 9 days. A community-based infection was suspected in 268 (57%) at admission; the diagnosis was confirmed in 96 patients (22%) and ruled out in 20 (4.2%); nevertheless, 152 patients (32%) received antibiotics on an empirical basis. A nosocomial infection was suspected in 63 (13.3%) of 453 patients and was confirmed in 59 (12.5%). The two most common community-acquired and nosocomial infections affected the respiratory and genitourinary tracts. Gram-negative bacteria were major etiological agents isolated. In the multivariate analysis, community-based infections associated with mucocutaneous, renal, or central nervous system disease activity as well as fever, and Mex-SLEDAI at admission and nosocomial infections to azathioprine use, infection at admission, disease duration, and hospitalization >7 days. We conclude that infections are an important cause of hospitalization of systemic lupus erythematosus patients. Risk factors include disease activity, use of immunosuppressants, disease duration, and length of hospital stay.

Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies and also by T-cell dysfunction. CD43 is expressed by most immune cells, is involved in lymphocyte adhesion and activation, and interacts with galectin-1 (Gal-1). The aim of this work was to evaluate the plasma levels of autoantibodies against CD43 and Gal-1 as well as the levels of soluble Gal-1 in SLE Mexican mestizo patients, with the aim of establishing a correlation between these parameters and the clinical profile. METHODS: Serum levels of immunoglobulin (Ig)G autoantibodies against CD43 and Gal-1 and levels of soluble Gal-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with SLE and 71 healthy controls. RESULTS: We found significantly enhanced titres of anti-CD43 and anti-Gal-1 antibodies in sera from SLE patients compared to controls. In addition, the serum levels of Gal-1 were significantly higher in SLE patients than in healthy individuals. However, we could detect no correlation of these parameters with disease activity [using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI)], age, or a variety of different clinical or laboratory features. Similarly, no significant correlation with immunosuppressive or glucocorticoid therapy was observed. By contrast, a significant association was found between anti-CD43 titres and time of disease evolution, complement levels, and the presence of anti-Gal-1 antibodies. CONCLUSIONS: As CD43 and Gal-1 participate in modulating the immune system, we suggest that the presence of autoantibodies against these molecules may contribute to the immune deregulation observed in SLE.

The use of methotrexate in children with rheumatic diseases.

Methotrexate (MTX) is one of the most useful drugs for the treatment of various rheumatic diseases in children, mainly juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and localised scleroderma. MTX is considered the standard treatment of JIA, particularly of those subgroups with polyarticular course. JIA response and remission rates to MTX are the standard for comparison with other drug modifying anti-rheumatic drug (DMARD) and biologic agents in clinical trials. On the other hand, short and long-term data suggest that MTX is a safety drug in the paediatric population with rheumatic diseases. Not surprisingly, MTX is the DMARD of choice in JIA either as monotherapeutic drug or in combination with biologic agents.

Association of HLA DRB1 alleles with juvenile idiopathic arthritis in Mexicans.

OBJECTIVE: The aim of the study was to investigate association between HLA class II alleles and juvenile idiopathic arthritis (JIA) in Mexican patients. PATIENTS AND METHODS: We typed 120 patients with JIA and 99 healthy controls for HLA class II alleles were performed by PCR-SSO. Differences between the whole group of JIA and its subtypes and controls were calculated by using the Xi2; p-values were corrected (pc) with Bonferroni's test. RESULTS: The alleles HLA-DRB1*01 (pc= 0.00083) and HLA-DRB1*04 (pc=0.0049) were strongly associated with systemic JIA, while HLA-DRB1*11 and HLA-DRB1*14 were found to have decreased frequencies in the patients with systemic JIA compared to the controls. Two alleles were found to have increased frequencies with JIA oligoarthritis subgroup, HLA-DRB1*11 (p=0.01, pc=NS) and HLA-DRB1*13 (p=0.01, pc=NS). The HLA-DRB1*04 was found increased frequencies with susceptibility for RF negative and RF positive polyarthritis JIA subgroups (p correction resulted in loss of significance). In contrast two alleles HLA-DRB1*07 and HLA-DRB1*14 were found decreased frequencies only patients RF positive polyarthritis JIA subgroup compared to the controls (pc=NS). CONCLUSION: The profile of HLA-DRB1 alleles associations in Mexican with JIA were somewhat distinct from association typically found in Caucasians.

The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis.

The field of spondyloarthritis (SpA) has experienced major progress in the last decade, especially with regard to new treatments, earlier diagnosis, imaging technology and a better definition of outcome parameters for clinical trials. In the present work, the Assessment in SpondyloArthritis international Society (ASAS) provides a comprehensive handbook on the most relevant aspects for the assessments of spondyloarthritis, covering classification criteria, MRI and x rays for sacroiliac joints and the spine, a complete set of all measurements relevant for clinical trials and international recommendations for the management of SpA. The handbook focuses at this time on axial SpA, with ankylosing spondylitis (AS) being the prototype disease, for which recent progress has been faster than in peripheral SpA. The target audience includes rheumatologists, trial methodologists and any doctor and/or medical student interested in SpA. The focus of this handbook is on practicality, with many examples of MRI and x ray images, which will help to standardise not only patient care but also the design of clinical studies.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal.

OBJECTIVE: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. METHODS: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as "paper patients" by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. RESULTS: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p<0.001) was strongly associated with the classification of axial SpA. The knowledge of MRI findings led to a change in the classification of 21.1% of patients. According to the first set of candidate criteria (sensitivity 97.1%; specificity 94.7%) a patient with chronic back pain is classified as axial SpA in the presence of sacroiliitis by MRI or x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). CONCLUSION: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.

Juvenile idiopathic arthritis. Subgroup characteristics and comparisons between rheumatoid arthritis-like subgroups and ankylosing spondylitis-like subgroups.

In terms of adult-onset definitions, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are rarely diagnosed in children. Adult RA is in most aspects similar to seropositive polyarticular arthritis in children, but AS differs in its clinical presentation according to age at onset. In general, the nomenclature and classifications of arthritis in children encompass subgroups with specific signs or laboratory tests and pathogenic mechanisms that distinguish one clinical form from the other. While one of these subgroups corresponds to RA, the one related to AS usually includes children with undifferentiated SpA and not definite AS. Thus, comparisons of RA and AS in children actually correspond to comparisons of various forms of childhood arthritis, currently classified as juvenile idiopathic arthritis (JIA) and AS in its early undifferentiated form. In this paper, we review these to finally compare the two populations.

Antibodies against recombinant heat shock proteins of 60 kDa from enterobacteria in the sera and synovial fluid of HLA-B27 positive ankylosing spondylitis patients.

OBJECTIVE: To study the association of HLA-B27 with IgG antibodies to different enterobacterial HSP60s in patients with ankylosing spondylitis (AS). METHODS: IgG antibodies to 60 kDa enterobacterial HSPs were determined by ELISA in paired samples of sera and synovial fluid from 21 HLA-B27+ ankylosing spondylitis (AS) patients; and in sera from 32 HLA-B27+ AS patients, 35 HLA-B27+ healthy relatives of AS patients, and 60 HLA-B27- healthy individuals with no family members with AS. RESULTS: HLA-B27+ patients and healthy individuals showed significantly higher IgG antibody levels to recombinant enterobacterial HSP60s than HLA-B27- healthy controls. The levels of anti-HSP60Sf and anti-HSP60Ec antibodies correlated with disease activity and anti-HSP60Ec antibodies with male gender. No association between enterobacterial HSP60 antibody levels and disease duration was observed. All groups had lower levels of IgG antibodies to rHSP60 from Streptococcus pyogenes (rHSP60 Spy). In paired samples of sera and synovial fluid from B27+ patients, IgG antibodies to enterobacterial HSP60s were detected, but in significantly higher levels in sera than in synovial fluid. The anti-rHSPSpy IgG response in these samples was lower and similar in the three groups. CONCLUSIONS: A correlation was found between HLA-B27 and the response to recombinat enterobacterial HSP60s. This response could be associated with disease activitir and gender in some proteins and the presence eof IgG antibodies to these proteins in synovial fluid could be associated with the inflammatory process and initiation of AS.

Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis.

OBJECTIVES: The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide. METHODS: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis. RESULTS: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%. CONCLUSIONS: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

Systemic features and early prognostic factors in Hispanic and non-Hispanic children from the United States of America and Mexico with systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate if the persistence of systemic features is longer in Hispanic children with systemic juvenile idiopathic arthritis (S-JIA) than in non-Hispanic children with S-JIA and to determine early predictors of systemic and articular disease. METHODS: We performed a multi-center retrospective chart review of patients followed in six pediatric rheumatology centers with onset of S-JIA from 1974 to 2004. Patients were included in the study if they had been followed for > or = 1 year after disease onset. Information collected included demographic, clinical, laboratory and treatment data. Systemic features included fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, and pleuritis. RESULTS: Of the 159 S-JIA patients screened, 120 (75%) met our inclusion criteria. There were 65 boys and 55 girls. The mean follow-up period for Hispanic patients was 5.7 years (SD 4.0) and for non-Hispanic patients was 8.6 years (SD 7.2). There was no significant difference in the presence of systemic features between Hispanic and non-Hispanic patients at 0.5, 1, 2, 4, 6, 8, and 10 years of follow-up. Polyarthritis at the 6-month visit was predictive of systemic features (OR 9.7, 95% CI 1.16-81.35, p = 0.036) and polyarthritis (OR 5.6, 95% CI 1.42-21.8, p = 0.014) at last follow-up. CONCLUSION: In children with S-JIA, Hispanics did not demonstrate longer persistence of systemic features than non-Hispanics. Polyarthritis at 6 months strongly predicted the development of persistent systemic features and chronic polyarticular disease.

Severe tophaceous gout. Characterization of low socioeconomic level patients from México.

OBJECTIVE: To describe a group of patients with frequent tophaceous gout, the variables associated with severe tophaceous gout and to compare them with other patients with gout described elsewhere. METHODS: We looked for 65 demographic clinical and paraclinical variables from patients with gout who attended our gout clinic from 1995-2000 and were evaluated by the same group of physicians. RESULTS: Three hundred and sixteen patients were included, 98% males, 82% live in México city, the mean age at onset, educational level and disease duration were 37.5 +/- 12.4, 6.3 +/- 3.9 and 12.6 +/- 10.3 years respectively. Tophaceous gout was present in 62% of the patients with a mean tophi number of 4.7 +/- 6.3 and mean HAQ score 0.13 +/- 0.37. Severe tophaceous gout (>or= 5 tophi) was found in 34% and these patients had significantly: earlier age at onset, longer duration of the disease, lesser frequency of obesity and higher frequency of: intradermal tophi, HAQ > 0.5, hospitalizations, radiographic score III/IV, uric acid under-excretion, renal function impairment and previous (oral and parenteral) auto-prescribed chronic glucocorticoid treatment compared with patients with non-severe tophaceous gout. In the multiple logistic regression the significant variables were renal function impairment (p = 0.000) and previous chronic parenteral glucocorticoid treatment (p = 0.011) . CONCLUSION: Our patients compared with those from other countries who have earlier age at onset, very low frequency of gout among females, frequent tophaceous gout and severe tophaceous gout. Severe tophaceous gout in this group is associated with renal function impairment and previous chronic parenteral glucocorticoid treatment.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

INTRODUCTION: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. METHODS: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. RESULTS: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. DISCUSSION: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

HLA antigens and juvenile onset spondyloarthritides: negative association with non-B27 alleles.

OBJECTIVE: To describe the association between HLA-B and HLA-DR genes and juvenile onset spondyloarthritides (SpA) in Mexicans. METHODS: The study included 66 consecutive patients with SpA (45 with ankylosing spondylitis (AS) and 21 with undifferentiated SpA) and 99 non-related healthy controls. The HLA-A, -B and DR alleles were detected by the polymerase chain reaction with the sequence-specific primers technique. Statistical methods included the Mantel-Haenzel chi2 test, Fisher's exact test, and Woolf method for odds ratio (OR). RESULTS: The frequency of HLA-B27 was significantly increased in the whole group (pC < 10(-3), OR = 53.0, aetiological fraction = 51%), particularly in AS (pC < 10(-3), OR = 67.42, aetiological fraction 57%). In contrast, the frequencies of HLA-B44, and HLA-B14 were significantly decreased. Also, a weak negative association HLA-DR5 (p < 0.05) was found. CONCLUSION: Apart from an expected significant association between HLA-B27 and juvenile-onset SpA, particularly AS, we found negative associations with HLA-B44, B14, and DR5. There was also a trend for HLA-B15 and DR1 associations with SpA.

Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset.

The aim of this study was to investigate the contribution of the different B27 subtypes in the Mexican Mestizo population with juvenile and adult AS. No differences in the distribution of B27 subtypes were found between both populations, B*2705 being the predominant subtype followed by B*2702. Transracial gene mapping was performed in order to find out the origin of the B27 alleles of the Mexican Mestizos. A PCR with SSOPs was used to analyze the polymorphism in exons 2 and 3 of HLA-B27 and HLA-C related alleles. This population shares with the Spanish Caucasians B*2705 and B*2702, which are absent in Central and South American Indians. AS and healthy Mexican mestizo donors were analyzed to ascertain B27/Cw haplotypes. The B27/Cw linkage arrangements seen in mestizos are similar to those reported for Caucasian Spaniards with three different haplotypes positively associated with AS in both populations, B*2705/Cw*0102, B*2705/Cw*02022, and B*2702/Cw*02022, suggesting that B27 in Mexicans may be due to a recent Caucasoid admixture with the Spanish genes. Finally, a strategy for sequence analysis of exons 2 and 3 from genomic DNA of HLA-B27 alleles was developed. A novel HLA-B27-like allele typed serologically as B27 was identified and sequenced by this method in a healthy Mexican mestizo, corresponding to the B*7301 variant found with low frequency in different populations. Analysis of the association of B*7301 to AS would require an extensive study in different populations and could provide insights into the molecular structure of the alleles involved in the disease.