Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis

OBJECTIVE: To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc). METHODS: Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, alpha/beta T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs). RESULTS: Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C-reactive protein levels (r(s) = -0.41, P = 0.001) and positively with CD19+ (r(s) = 0.35, P = 0.001) and CD20+ (r(s) = 0.34, P = 0.002) lymphocyte counts. CONCLUSION: B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.     

Contribution de la Screen for Child Anxiety Related Emotional Disorders au dépistage et au diagnostic des troubles anxieux chez l’enfant d’âge scolaire

Children's anxiety disorders were for a long time viewed as poorly differentiated; however, many researchers recently brought evidence that syndromes similar to adult ones are clearly recognizable among very young children. The best instruments for diagnosing these disorders are time-consuming structured interviews like the Schedule for Affective Disorders and Schizophrenia for School Age Children (Kiddie-SADS). Is it possible to shorten the diagnostic procedure using “paper/pencil” questionnaires as diagnostic tests? The aim of this study was to test the diagnostic value of the Screen for Child Anxiety Related Emotional Disorders (SCARED), which comprises a self-report form and a parent-report form, and assesses four DSM anxious disorders. We examined 69 children aged 6 to 12 (36 boys) addressed to a school psychology facility using both self-report and parent-report SCAREDs and Kiddie-SADSs. Indices were defined, based on threshold-scores on the four SCARED syndrome scales. Theses indices all showed high sensitivity, but have different specificities: maximal for separation anxiety disorder, moderate for panic disorder and social phobia, but poor for generalized anxiety disorder. The SCARED-based indices performed well as screen for these four anxious disorders. In addition, they allow substantial time economy in the process of diagnosing separation anxiety disorder, panic disorder, and social phobia.     

Urinary free light chain analysis by the Freelite immunoassay: a preliminary study in multiple myeloma

Evaluate the Freelite free light chain immunoassay for urine analysis in myeloma.Urine specimens from 20 patients were analyzed by Freelite (The Binding Site) and SDS-agarose gel electrophoresis (Hydragel protéinurie, Sebia).Using the kappa/lambda ratio, Freelite was more sensitive than electrophoresis to detect free light chains, but concentration was overestimated in 75% of cases.Despite high sensitivity and full automation, Freelite inaccurately measures monoclonal free light chains in urine.     

Autoimmune cytopenias associated with autoantibodies to nuclear envelope polypeptides

A subset of anti-nuclear autoantibodies (ANA) are directed against nuclear envelope (NE) polypeptides and display by indirect immunofluorescence (IIF) a ring-like fluorescent pattern. We report herein 19 patients with autoimmune cytopenias associated with antibodies (Abs) to NE polypeptides. Anti-NE specificity was determined by immunoblot, using NE preparations and purified lamina fractions. Eleven sera reacted with lamin B(1), and two reacted with both lamin B(1) and an unidentified 150-kDa protein (p150). One serum reacted with only p150. Four sera reacted with lamins A and C, and one reacted with and an unidentified 52-kDa NE polypeptide (p52). Autoimmune cytopenias included hemolytic anemia (7 cases), thrombocytopenia (13 cases), and neutropenia (6 cases). Five patients had 2 (3 cases) or 3 (2 cases) different cytopenias. Antiphospholipid antibodies (APLA) were detected in 14 patients, 2 of whom experienced thromboembolic events. A liver disorder was present in 7 patients. Systemic lupus erythematosus and lupus-like syndrome were diagnosed in 11 and 2 patients, respectively. Cytopenias responded to steroids alone (13 patients), or together with intravenous immunoglobulins (2 patients), or cyclophosphamide (2 patients). Two patients did not require treatment. Our results suggest that anti-NE Abs need to be sought for in patients with peripheral cytopenias, particularly when they are associated with APLA and/or liver disorders. Their detection strongly suggests an autoimmune process. Such cytopenias are often manifestations of a lupus or lupus-like disease and are responsive to steroids.     

Anti-p53 antibodies are rarely detected in serum of patients with rheumatoid arthritis and Sj?gren's syndrome.

OBJECTIVE: To detect evidence of abnormalities of the p53 protein in autoimmune diseases. Mutation of the p53 protein may inhibit apoptosis and thereby lead to cancer and possibly play a role in the pathogenesis of autoimmune diseases. METHODS: Serum antibodies to p53 are detected in 30 to 50% of patients with cancer who have p53 mutations. Using an ELISA, we determined the prevalence of anti-p53 antibodies in the serum of 106 patients with rheumatoid arthritis (RA), 72 patients with primary Sj?gren's syndrome (SS), and 14 patients with lymphoma complicating SS. The presence of anti-p53 antibodies was also measured in the synovial fluid of 16 patients with RA. Positive sera by ELISA were confirmed by immunoprecipitation. RESULTS: Serum anti-p53 antibodies were detected in 2 of 106 patients with RA. The synovial fluid of one of these 2 patients was also studied and was positive. Anti-p53 antibodies were not detected in the other synovial fluids. Serum anti-p53 antibodies were not detected in 72 patients with primary SS alone, but were present in 2 of 14 patients with lymphoma complicating SS. CONCLUSION: Our results suggest that if p53 mutations have any role in the pathogenesis of some autoimmune diseases, they are rarely associated with the presence of anti-p53 antibodies in patients with RA. In patients with SS, the presence of serum anti-p53 antibodies might be an indirect sign of the development of a lymphoma.     

Behavioral and emotional problems of Algerian children and adolescents as reported by parents

Objective To determine the level of behavioral and emotional problems among a sample of Algerian children and adolescents aged 6–18 years living in Algiers. Methods A school-based sample of 1,405 children and adolescents was recruited; problems were assessed with the Child Behavior Checklist filled out by parents or surrogates. Results The scores varied with age, gender, and socioeconomic status (SES). Contrary to findings in other samples, most Problem scores increased with age. As found in many other cultures, girls scored higher than boys on the Internalizing scales, but lower on Externalizing scales. Youths from lower socioeconomic families tended to score higher on some Problem scales. But, above all, Algerian children and adolescents had raw scores on all Problem scales much higher than those yielded by most previous cross-cultural studies. Conclusions The high level of problems may be attributable to traumatic environmental factors (terrorism and natural catastrophes), but the lack of data from countries that have similar geographic and cultural environments makes it hard to exclude explanations based on cultural factors.