ABSTRACT
To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.
Subject(s)
Arthritis, Rheumatoid/complications , Cognitive Dysfunction/complications , Cytokines/metabolism , Lymphocyte Subsets/immunology , Nerve Growth Factors/metabolism , Adult , Aged , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/psychology , Cognitive Dysfunction/immunology , Cognitive Dysfunction/psychology , Cross-Sectional Studies , Female , Flow Cytometry , Humans , Immunophenotyping , Male , Middle Aged , Neuropsychological TestsSubject(s)
Adrenal Cortex Hormones/therapeutic use , Arthritis, Rheumatoid/drug therapy , Hepatitis, Viral, Human/diagnosis , Herpes Simplex/diagnosis , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Aged , Causality , Drug Therapy, Combination , Female , Hepatitis, Viral, Human/epidemiology , Hepatocytes/pathology , Hepatocytes/virology , Herpes Simplex/epidemiology , Herpesvirus 1, Human/isolation & purification , Humans , Immunocompromised HostABSTRACT
OBJECTIVE: To systematically review the evidence of the association of anticardiolipin antibodies with preeclampsia. DATA SOURCES: PubMed and LILACS were perused up to June 2009, citations were searched using the ISI Web of Knowledge database, textbooks and reference lists were reviewed, and experts were contacted. Search terms included "antiphospholipid syndrome," "Hughes' syndrome," "anticardiolipin antibodies," "antiphospholipid antibodies," "anti-cardiolipin," "preeclampsia," and "pre-eclampsia." METHODS OF STUDY SELECTION: Inclusion criteria were: cohorts, case-control, or controlled cross-sectional studies; healthy pregnancy as controls; no autoimmune diseases; immunoglobulin (Ig)G, IgM anticardiolipin antibody of at least 20 units by enzyme-linked immunosorbent assay, or both; and end-point preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Our search generated 68,528 entries and 64 full-text articles were reviewed. Twelve studies were included in the meta-analysis. Pooled odds ratio (OR) for association of anticardiolipin antibodies with preeclampsia was 2.86 (95% confidence interval [CI], 1.37-5.98). Pooled OR for anticardiolipin antibodies and severe preeclampsia was 11.15 (95% CI 2.66-46.75). Funnel plot showed minor asymmetry, and the Egger test was not significant (P=.359). Meta-regression identified study design and size as related to heterogeneity. CONCLUSION: Moderate-to-high levels of anticardiolipin antibodies are associated with preeclampsia, but there is insufficient evidence to use anticardiolipin antibodies as predictors of preeclampsia in clinical practice.
