Prognostic markers of clinical remission in early rheumatoid arthritis after two years of DMARDs in a clinical setting.

OBJECTIVE: To analyze the rate and baseline prognostic factors of clinical remission in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy based on a structured algorithm using disease-modifying anti-rheumatic drugs (DMARDs) in a clinical setting. To determine whether a good therapeutic response at 6 months of therapy is associated with remission at 2 years. METHODS: One hundred and five patients (81% female) with early RA (disease duration < 2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was clinical remission after 2 years of DMARD therapy using the 28-joint disease activity score (DAS28 < 2.6). Clinical, biological, immunogenetic and radiographic data (Larsen score) were analyzed at study entry and after 6, 12, 18 and 24 months of follow-up. Therapeutic response was analyzed using the ACR and EULAR criteria. RESULTS: Remission was observed in 34 patients (32.4%) after 2 years of follow-up. A baseline DAS28 score < 5.1 (p = 0.004), hemoglobin (p = 0.04) and male gender (p = 0.02) were associated with remission in the univariate analysis. In the multivariate logistic regression analysis, only a DAS28 < 5.1 was associated with remission at 2 years (OR 4.1, 95% CI: 1.56;10.77, p = 0.004). The percentage of ACR50 responses after 6 months was significantly higher in patients with remission at 2 years than in those without (66.7% vs 43.3%; p = 0.04). Similar results were obtained when analyzing the good EULAR response (50% vs 20.9%; p = 0.003). Furthermore, when the therapeutic response at 6 months was included in the logistic regression model, only an ACR50 response (OR 3.9, 95% CI 1.14;13.38, p = 0.03) and a good EULAR response (OR 6.23, 95% CI 1.61; 24.04, p = 0.008), but not an ACR20 response or a whole EULAR response were significantly associated with remission. CONCLUSION: In a series of early RA patients treated using a structured algorithm with DMARDs and very low doses of glucocorticoids, clinical remission was observed in one-third of patients after 2 years. Low or moderate disease activity (DAS28 < 5.1) at baseline and a good therapeutic response during the first months of therapy predicts clinical remission at 2 years.

Relevance of MICA antibodies in acute humoral rejection in renal transplant patients.

The presence of MICA antibodies was examined in eleven patients diagnosed with AHR. MICA typing was performed in both recipients and donors. Sera were collected sequentially: pre-transplant, at the AHR episode and at follow-up. Sera from 30 patients with functioning graft were also analysed. A stable MICA()008 transfected cell line was used as target to identify MICA antibodies. MICA antibodies were not detected pre-transplant nor post-transplant in patients receiving a compatible graft. MICA antibodies were detected post-transplant AHR in patients receiving an incompatible graft. The persistence of MICA antibodies was associated with chronic graft dysfunction in 3 of 4 patients in this series; although it was not always associated with the graft loss in treated AHR. None of the 30 patients in the control group with long-term functioning grafts showed antibodies to MICA()008. This report provides some insights of the relevance of MICA antibodies in AHR.

[Susceptibility to chronic HLA-system-associated lymphocytic thyroiditis. Its relationship with insulin-dependent diabetes mellitus]. / Susceptibilidad a tiroiditis crónica linfocitaria asociada al sistema HLA. Su relación con la diabetes mellitus insulinodependiente.

The genetic association between HLA-system and chronic lymphocytic thyroiditis (CLT) related or not to type I diabetes mellitus (IDDM), have been analysed in three groups of children: 16 with CLT, 9 with CLT and IDDM, 11 with IDDM and 200 normal controls. The DQw1 antigen (75% vs 55%) was found associated with CLT, furthermore the observed increase of DR1 and DR2 antigens (37% respectively) is secondary to the linkage disequilibrium that exists between them and DQw1. DR3 antigen (60%) was found significantly increased (p less than 0.001) in CLT patients compared with the control group (24%). In diabetic patients, DR3 and DR4 were found in 85% and 63% respectively (p less than 0.001). The DR3 associated haplotype in CLT patients was different from the diabetic one's. All the diabetics, but one, were DR3-B18 haplotype carriers, but this association was only found in 25% CLT patients. The titre of thyroid microsomal antibodies (MCHA) was more frequent in the patients with DQw1 antigen (MCHA DQw1+ : 1/1072; DQw1- : 1/606). The CLT predisposition in childhood may be influenced by genes located within the HLA-region probably more than one, different from the genes related to IDDM. One of this genes closed to the HLA-DQ region, will be involved in the production of autoantibodies.

[Familial study for the early diagnosis of insulin-dependent diabetes mellitus]. / Estudio familiar para el diagnóstico temprano de la diabetes mellitus insulinodependiente.

BACKGROUND: Diabetes is more frequently found than expected in families of first grade with children with diabetes type I. METHODS: With the aim of identifying the potential candidates prone to develop diabetes type I, genetic and metabolic analysis was carried out on the members of 11 families with a diabetic type I child. They were distributed into three groups: 11 diabetic patients (IDDM); 22 progenitors and 13 unaffected siblings. The HLA haplotype was determined, the spectrum of autoantibodies and the intravenous glucose tolerance test (IVTT) were performed. RESULTS: In two progenitors postprandial glycemia values corresponding to intolerance to carbon hydrates were obtained. Moreover, in one the IVTT was found to be low in the normal values. Of a total of 12 non diabetic descendents studied, 4 shared identical HLA haplotypes as the diabetic, 5 were haploidentical and 3 unidentical. The DR 3 antigen was detected in 90% of the diabetics; in 68% of the progenitor group and in 50% of the non diabetic descendents. Sixty-two percent of the children inherited the DR 4 antigen of the father (p less than 0.05), while 37% do so from the mother. Of the siblings with a haplotype identical to that of the diabetic, 2 were also ICA positive; asymptomatic at the moment of the study but in one the diabetes type I became manifest after 2 years of evolution. CONCLUSIONS: Subjects at high risk of becoming type I diabetics may be identified at a preclinical phase by means of HLA typing and the detection of immunologic and metabolic markers associated with the disease.

HLA antigens in Forestier's disease, ankylosing spondylitis, and polyarthrosis of the hands.

HLA antigens were studied in three different groups of 50 patients each. These included (a) Forestier's disease, (b) ankylosing spondylitis, and (c) polyarthrosis of the hands. HLA typing included 12 specificities from locus A and 15 from locus B, the frequencies being compared to those in 700 normal controls. No significant differences were found in the frequency of distribution between the polyarthrosis patients and the normal population. In patients with Forestier's disease, B5 was increased, but this was not a significant difference. The antigen B27 was present in 94 per cent of patients with ankylosing spondylitis, confirming previous studies.

The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection.

OBJECTIVES: To investigate the role of C282Y and H63D mutations, and hepatitis C virus (HCV) infection in the pathogenesis of porphyria cutanea tarda (PCT). DESIGN: Prospective case-control study. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases in Barcelona, Spain. PATIENTS: Ninety-nine consecutive patients with PCT and one hundred and twenty-six control patients (76 healthy subjects and 50 patients chronically infected with HCV), were recruited. MAIN OUTCOME MEASURES: The frequency of the C282Y and H63D mutations in patients with PCT vs. controls and the relationship of these mutations with HCV infection, and iron status, as judged by serum iron, liver iron and ferritin levels. RESULTS: C282Y mutation was significantly increased in PCT patients. This mutation was more frequent among non-HCV-infected patients. Increased ferritin levels and hepatic iron overload were also observed in PCT patients with heterozygous C282Y state. H63D mutation was only significantly increased among PCT patients with chronic hepatitis C infection. No significant iron overload was observed in patients with H63D mutation. CONCLUSIONS: This study confirms the high frequency of C282Y mutation in patients with PCT and its relationship with iron overload. The C282Y mutation has a relevant role in Spanish patients with PCT not associated with HCV chronic infection. On the other hand, the prevalence of the H63D mutation seems not to be increased in patients with PCT. The possibility of an association between HCV infection and H63D mutation in inducing PCT can be hypothesized.

[Use of FMC macromolecular medium for determination of the erythrocyte ABO group using microtiter plates]. / Empleo del medio macromolecular FMC para la determinación del grupo eritrocitario ABO empleando placas de microtitulación.

Several blood group determination techniques have been developed in recent years which provide easy handling, fine reproducibility and similar or even higher sensitivity than the procedures commonly employed, aimed to be used in the automation of blood bank work. A microtitration plate technique for ABO determination on red cells is presented in this report. A macromolecular medium, comprised of a mixture of the polymers Ficoll 400 and carboxymethyl cellulose (FMC) is used ad coadjuvant for the reaction. This medium increases by 15- the score units and by 4-fold (or more) the intensity of haemagglutination (titration) in typing the ABO antigenicity of red cell A, B, O and AB groups.

HLA antigens in a family with both parents and several siblings affected by Graves' disease.

A family with autoimmune thyroid disease is described. Four members had Graves' disease and 3 had diffuse goitres. Both parents (second cousins) carry the HLA haplotype: HLA Aw24, Bw39(w6), Cw-, DR3, MT2. Only females with this haplotype show thyroid symptoms. These findings emphasize the involvement of HLA linked genes in susceptibility to Graves' disease.

[Study of anti-DR antibodies in sterility and infertility (author's transl)]. / Análisis de los anticuerpos anti-DR des sistema HLA en la esterilidad e infertilidad.

The presence of anti-DR antibodies with lymphocyte cytotoxicity test was studied in five groups of patients: 50 males with no history of blood transfusions who comprised the control group, 44 contraceptive-using women, 55 pregnant women, 41 primary sterile and 47 infertile patients. The high and similar degree of sensitization found in both pregnant and sterile patients lead us to the conclusion that anti-DR antibodies are not a cause of sterility and that spermatozoa are highly immunogenic. The biological significance of the antibodies is discussed.

HLA class II antigens (DR, DQ loci) and peripheral arthritis in ankylosing spondylitis.

Fifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.

Hepatitis C virus infection in patients with nonalcoholic chronic liver disease.

STUDY OBJECTIVE: To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN: Cross-sectional study. SETTING: The liver unit of a referral-based university hospital. PATIENTS: Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS: In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS: Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.