Distinguishing features of anti-beta2 glycoprotein I antibodies between patients with leprosy and the antiphospholipid syndrome

Anticardiolipin (ACA), anti-beta2 glycoprotein I (beta2GPI), and antiprothrombin antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent assays in 176 untreated leprosy patients across the histopathological spectrum. Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus 4% in healthy controls (p <10(-2) to 10(-3)). Levels of IgM anti-beta2GPI and IgG ACA were significantly higher in lepromatous leprosy and multibacillary patient subgroups. IgG3 was the most common subclass reactive to both beta2GPI and prothrombin in selected high-titer leprosy sera, unlike antibodies from patients with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy patients, but not in the APS control group, there was no statistical correlation between ACA and anti-beta2GPI antibody levels. Likewise, a large fraction of anti-beta2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were unreactive in the standard ACA assay. Most assayed anti-beta2GPI antibodies from leprosy patients showed (i) ability to recognize both human and bovine beta2GPI immobilized on non-irradiated polystyrene plates, (ii) concentration-dependent inhibition of binding by cardiolipin, and (iii) relatively high avidity binding to fluid-phase beta2GPI, thereby differing from those found in APS. Finally, the location of the major epitopic region on the beta2GPI molecule targeted by autoantibodies was different in leprosy and APS, as assessed by direct binding to domain I- and V-deleted mutants and competition with the mouse monoclonal antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid antibodies comprise persistent IgG and IgM anti-beta2GPI that differ from APS-related ones with respect to IgG subclass, avidity and epitope specificity, possibly reflecting distinct pathophysiological significance.     

Serological abnormalities, including common idiotype PR4, in families with rheumatoid arthritis.

A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.     

Monoclonal immunoglobulins in the serum of patients with primary Sj?gren's syndrome

Monoclonal immunoglobulins (M Igl) were detected in the serum of 10 of 20 patients with primary Sj?gren's syndrome (prim. SS), by using high resolution electrophoretic technique combined with immunofixation. The finding of three free lambda chains and two IgG lambda suggests that the lambda-expressing B-clones are involved in this process, but the class distribution is different from one series to another, and from one country to another. The prim. SS patients with multiogran disease have the higher incidence of M Igl.     

Relation of antivimentin antibodies to anticardiolipin antibodies in systemic lupus erythematosus.

Tests for antivimentin antibodies (AVA) were performed on 50 systemic lupus erythematosus (SLE) and 63 control sera by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA). The prevalence was significantly raised in SLE (38% and 50% of sera positive for IgM-AVA and IgG-AVA, respectively, by immunofluorescence; 36% and 64% of sera positive for IgM-AVA and IgG-AVA, respectively, by ELISA) in comparison with the control sera. A significant correlation existed between IgM-AVA, on the one hand, and anticardiolipin antibodies (ACA) and anti-single-stranded DNA (ssDNA), on the other. A stepwise principal component analysis demonstrated that IgM-AVA and IgG-AVA accounted for 71% of the total variance in SLE (50 patients x 5 parameters = total variance). Twenty ACA positive serum samples from patients with syphilis were therefore tested for the presence of AVA, but hardly any were found to be positive. IgM-AVA from patients with SLE were inhibited by cardiolipin and absorbed with ssDNA. An association between AVA positivity and arthralgia was also shown in SLE.     

Enhanced sialyltransferase activity in B lymphocytes from patients with primary Sjögren's syndrome

Despite the indisputable role of immunoglobulin (Ig)A in the pathogenesis of primary Sjögren syndrome (pSS), the causative abnormality remains largely unknown. As an extension of our report that IgA is oversialylated in this disease, the thrust of the present study was to measure the sialyltransferase (ST) activity in B lymphocytes. ST containing lysates of B cells from 17 pSS patients and 10 controls, were obtained using a combination of detergents, and incubated with affinity purified IgA that had been previously desialylated. The deposition of cytidine 5′ monophosphate sialic acid (SA) by ST from B cells onto IgA was detected by two ELISA based upon the use of biotinylated lectins (Sambucus nigra agglutinin which is specific for α2–6 SA and Maackia amurensis which is specific for α2–3 SA). In parallel, the amount of SA on IgA from ten of the 17 patients and eight of the 10 controls was assayed using the same method. An excess of α2–3 and α2–6 SA on IgA was found in those patients with excessive activity of α2–3 and α2–6 ST. Thus, IgA hypersialylation in pSS patients may result from undue activity of ST.     

Non-invasive positive pressure ventilation in acute respiratory failure: providing competent care

Non-invasive positive pressure ventilation (NPPV) has been used as an alternative strategy to provide ventilatory support for patients with acute respiratory failure. Most studies demonstrate that the use of NPPV in acute respiratory failure results in a reduction in the need for endotracheal intubation and an overall survival advantage. However, current evidence, in the form of randomized controlled trials, suggests that these benefits may be restricted to patients suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD).

The clinical application of NPPV involves the development of competence in delivering the particular intervention. Clinical outcomes and thus valid comparisons with alternate methods of ventilatory support can only be made if attention is paid to the clinical indications for the application of NPPV and patient subgroups it is used to treat and the level of competence of care givers in its application and delivery. One essential element of competence is the establishment of an appropriate knowledge base and the development of clinical practice guidelines. This literature review identifies the current indications for NPPV and the relevant information for developing clinical practice guidelines for the management of this form of ventilatory support.     

Sunlight Exposure and Breast Density: A Population-Based Study

Purpose

This study aims to assess the association of sunlight exposure with breast cancer risk, measured by the breast density assessed from Tabár''s mammographic pattern in Chinese women.

Methods

A total of 676 premenopausal women were recruited to participate in this study, in which 650 completed a validated sunlight exposure questionnaire via telephone. The mammograms were classified according to Tabár''s classification for parenchyma, and patterns IV & V and I, II & III indicated respectively high and low risk mammographic patterns for breast cancer. The odds ratios (OR) and 95% confidence intervals (CIs) for sun exposure-related variables were estimated using unconditional logistic regression with adjustment for potential confounders.

Results

Among 646 participants, women with high breast cancer risk (Tabár''s patterns IV &V) had less hours spent in the sun than those with low risk (I, II & III) at any age stage. A higher level of sunlight exposure was associated with a significantly lower risk having high risk Tabár''s pattern. Women aged 40 to 44 years who were in the highest tertile of lifetime total hours spent in the sun had a multi-adjusted OR of 0.41 (95% CI, 0.18-0.92; p for trend=0.03) compared with those in the lowest tertile (>2.19 hr/day vs. <1.32 hr/day). For hours spent in the sun across the ages of 6 to 12 years, the comparable OR was 0.37 (95% CI, 0.15-0.91; p for trend=0.03).

Conclusion

These findings suggest that higher sunlight exposure is related to a lower risk of having high risk breast density pattern in premenopausal women. Our results also suggest the most relevant period of exposure is during earlier life.     

Cardamonin inhibits pro-inflammatory cytokine production and suppresses NO pathway in PBMCs from patients with primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C₁₆H₁₄O₄), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS. For this purpose, peripheral blood mononuclear cells isolated from pSS patients and healthy controls were cultured with different concentrations of cardamonin. Cytokine levels were measured by ELISA and NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence staining. Our results suggest that cardamonin inhibits TNF-α, IL-6 and NO production and downregulates iNOS expression and NF-κB activation. Collectively, our results highlight the ex vivo immunomodulatory effects of cardamonin on pro-inflammatory cytokine production and NO pathway in pSS patients. Therefore, cardamonin is a potential candidate for controlling inflammation during pSS.