Ajax Mercês Atta

Immunoglobulin E and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by intense polyclonal production of autoantibodies and circulating immune complexes. Some reports have associated SLE with a Th2 immune response and allergy. In the present study 21 female patients with SLE were investigated for total IgE and IgE antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent assay, and were also evaluated for antinuclear IgE autoantibodies by a modified indirect immunofluorescence test using HEp-2 cells as antigen substrate. Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median = 394 IU IgE/ml), was observed in 7 of 21 SLE patients (33%), 5 of them presenting proteinuria, urinary cellular casts and augmented production of anti-dsDNA antibodies. While only 2 of 21 SLE patients (9.5%) were positive for IgE antibodies to aeroallergens, all 10 patients with respiratory allergy (100%) from the atopic control group (3 males and 7 females), had these immunoglobulins. SLE patients and healthy controls presented similar anti-IgE IgG autoantibody titers (X = 0.37 +/- 0.20 and 0.34 +/- 0.18, respectively), differing from atopic controls (0.94 +/- 0.26). Antinuclear IgE autoantibodies were detected in 17 of 21 (81%) sera from SLE patients, predominating the fine speckled pattern of fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can present increased IgE levels and antinuclear IgE autoantibodies without specific clinical signs of allergy or production of antiallergen IgE antibodies, excluding a possible association between SLE and allergy.

Autoimmune Response of IgE Antibodies to Cellular Self-Antigens in Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus (SLE) patients may exhibit high total IgE and antinuclear IgE antibodies (ANA-IgE). Here, we investigated the specificity of ANA-IgE in SLE patients and the involvement of cytokines in this immune response. Methods: Sera from 92 SLE patients and 68 healthy controls were evaluated for the presence of antinuclear IgE antibodies by immunoperoxidase with HEp-2,000® cells and immunoblotting with IgG-depleted sera. Total IgE, IgE specific to allergens, and serum cytokine levels were determined by ELISA. Results: Antinuclear IgE antibodies were detected only in SLE patients (29/92, 31.5%). High total IgE was associated with ANA-IgE (p < 0.0001), but was not associated with IgE antibodies to allergens. In the immunoblotting, ANA-IgE reacted with nucleosomes (23/29, 79.3%), dsDNA (14/29, 48.3%), SS-A/Ro (14/29, 48.3%), SS-B/La (2/29, 18.7%), Sm (14/29, 48.3%) and RNP (18/29, 62.1%). Patients with ANA-IgE had very low serum IL-4, less IL-5 than controls (p < 0.05), more IL-10 than seronegative patients (p < 0.05), and unaltered IFN-γ levels. The IL-5/IL-10 ratio was lower in ANA-IgE seropositive patients in comparison with either seronegative patients (p < 0.05) or healthy controls (p = 0.001). Controls displayed higher IL-5/IFN-γ ratios than either SLE patients with ANA-IgE (p < 0.05) or patients without these immunoglobulins (p < 0.01). Conclusions: We conclude that IgE antibodies against cell autoantigens involved in protein expression, cellular proliferation, and cell death are present in patients with SLE. Interleukin-10 seems to down-regulate this IgE autoimmune response in SLE.

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

Low frequency of positive skin tests in asthmatic patients infected with Schistosoma mansoni exposed to high levels of mite allergens.

Helminthic infections and allergic diseases are highly prevalent in many parts of the world. Although skin reactivity to indoor allergens is decreased in subjects from helminthic endemic areas, the degree of exposure to mite allergens has not yet been investigated in these areas. This study evaluated the association between exposure to dust mites and skin reactivity to mite allergens in subjects with a history of wheezing in the last 12 months selected from a rural endemic area for schistosomiasis (group I, n = 21), and two non‐Schistosoma mansoni endemic locale, a rural area (group II, n = 21) and a urban slum area (group III, n = 21). All subjects were evaluated by skin prick tests with mite allergens, and for total and specific immunoglobulin E (IgE) against dust mites, antibodies for S. mansoni, and for intestinal parasites. Dust samples from each subjects’ home were quantified for mite allergen and species of the mite identification. Except for S. mansoni infection which was more prevalent in group I than in groups II and III (p < 0.0001), the prevalence of intestinal parasites, and total and specific IgE levels were similar for all groups. Despite the levels of mite allergens and specifically to Der p 1 detected in dust samples of subjects home from all three areas, the frequency of positive skin reactivity to mite antigens was significantly lower (19.0%) in subjects from group I relative to group II (76.2%) and group III (57.1%; p < 0.001). This result suggests that S. mansoni infection could modulate the immediate hypersensitivity skin response to mite allergens in highly exposed subjects.

Profile of autoantibodies in Jaccoud's arthropathy.

OBJECTIVE To compare the frequency of different autoantibodies in a group of patients with Jaccouds arthropathy (JA) secondary to systemic lupus erythematosus (SLE) with those without JA. METHODS A group of SLE patients with JA was compared with another group of SLE patients without this complication, matched by age and gender, regarding the presence of autoantibodies. Antibodies to cyclical citrullinated peptides (anti-CCP) and to mutated citrullinated vimentin (anti-MCV) as well as anti-SSA/Ro, anti-SSB/La, anti-Sm and anti-RNP and anticardiolipin (aCL) antibodies were searched by ELISA, using commercial kits. Rheumatoid factor was determined by nephelometry and antinuclear and anti-dsDNA antibodies by IIF. RESULTS Forty-eight individuals were included in the study, being 24 patients with JA and 24 without JA, matched by gender and age. The frequency of anti-CCP antibodies in the whole population was 12.5% (6 cases), with no difference between the 2 groups. Anti-MCV antibodies were detected in 10.4% (5 cases), being found only in those with JA (p=0.05). There was no association between the presence of JA and aCL, anti-Sm, anti-RNP and anti-SSB/La antibodies. On the other hand, a statistically significant association between the presence of anti-dsDNA antibodies and JA was observed (p=0.04) as well as a marginal association with a decrease in serum levels of C3 (p=0.06). CONCLUSION In the present study, there was an association between the presence of JA and anti-dsDNA antibodies, and anti-MCV antibodies were found only in those SLE patients with JA. Whether these antibodies have an etiopathogenic role in JA is entirely unknown.

Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-β and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4 pg/mL; HCV=96.8 pg/mL, p<0.001) and IL-8 (controls=30.1 pg/mL; HCV=18.1 pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5 pg/mL) than did patients with high HCV loads (16.7 pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

OBJECTIVE To investigate the frequency of thyroid disorders (TD) in patients with chronic hepatitis C before and during interferon-alpha (IFN-α) and ribavirin (RIB) treatment. STUDY DESIGN Prospective study. PATIENTS AND METHODS We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of treatment. RESULTS Mean age of the 65 patients (38 females and 27 males) was 49.61 ± 11.83 years. Seven (10.76%) patients presented baseline thyroid disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92%) patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A total of 18 patients (27.69%) developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6), hyperthyroidism 1.2 (95% CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5). The study showed a significant association between female sex and thyroid disease (p = 0.009). CONCLUSION Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

Autoimmunity in hepatitis C virus carriers: Involvement of ferritin and prolactin

BACKGROUND Ferritin and prolactin have been associated with active autoimmune diseases as systemic lupus erythematosus and autoantibody production, but have been little studied in viral infections that present autoimmunity. OBJECTIVE To investigate the association of these two autoimmune mediators with the presence of cryoglobulinaemia and non-organ-specific autoantibodies (RF, SMA, β2GPI IgA antibody and ANA) in Brazilian individuals chronically infected with hepatitis C virus (HCV). METHODS Ninety-nine patients were evaluated. Ferritin and prolactin levels were determined by chemiluminescent immunoassays. RESULTS Hyperprolactinemia was found in 10 (six men and four women) out of 99 (10.1%) hepatitis C patients. Thirty-eight out of 99 (38.4%) HCV carriers had hyperferritinemia (median level 385ng/mL). Neither hyperprolactinemia nor hyperferritinemia was associated with cryoglobulinaemia or non-organ-specific autoantibodies (p>.05). There was an association between hyperprolactinemia and the infection with HCV genotype 3 (p<.01). Ferritin and ALT levels were correlated (p<.05). CONCLUSION Our results suggest that neither prolactin nor ferritin is involved with the extra-hepatic manifestation of autoimmunity observed in HCV carriers.

Serum cytokine profile in hepatitis C virus carriers presenting cryoglobulinaemia and non-organ-specific autoantibodies

This work investigated the serum cytokine profile (IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF) of hepatitis C virus (HCV) carriers with autoimmunity. Forty-seven HCV carriers and 28 healthy controls were evaluated. Cytokine levels were measured by ELISA. Patients and controls presented similar levels of IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF (p>0.05). Cryoglobulinaemic HCV carriers had increased IL-2 (p=0.013), IL-5 (p=0.018) and BAFF (p=0.050). IFN-gamma level was decreased in HCV carriers with rheumatoid factor in comparison with those that were RF-seronegative (p=0.035). Patients with beta2GPI IgA antibodies when were compared with those without this autoantibody, had more serum IL-2 (p=0.009), IL-5 (p=0.018) and BAFF (p=0.039). Interleukin-2 was increased in HCV carriers with positive ANA when they were compared with ANA-seronegative carriers (p=0.044). Interleukins IL-4 and IL-10 were not associated with autoimmunity (P>0.05). In HCV carriers, IL-2 was correlated with IL-5 (p<0.0001) and IFN-gamma (p=0.015), and IL-5 with IFN-gamma (p=0.015). We concluded that the serum profile of cytokines in HCV carriers presenting autoimmune markers may be mainly represented by increased IL-2, IL-5 and BAFF.

Study of autoantibodies in patients with keratoconjunctivitis sicca infected by the human T cell lymphotropic virus type 1

Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in many regions of the world, including Brazil, and has been associated to several immunological manifestations such as arthritis, uveitis, dermatitis and Sjögren’s syndrome. This study was intended to evaluate the frequency of autoantibodies in patients infected with HTLV-1 and manifesting keratoconjunctivitis sicca (KCS). HTLV-1 patients with KCS, enrolled in a reference ambulatory of the city of Salvador, were tested for autoantibodies such as antinuclear antibodies, rheumatoid factor, anti-SSA/Ro and anti-SSB/La. Two comparison groups were also included: (a) HTLV-1 patients without KCS and (b) seronegative patients with KCS. Correlation of proviral load (PVL) in HTLV-1 patients with presence or absence of KCS was also assessed. No autoantibodies were detected in HTLV-1 patients with KCS. The PVL of HTLV-1 patients was higher in patients with KCS without other clinical manifestations customarily associated to HTLV-1. In conclusion, in this study, no changes were observed in humoral immunity concerning production of certain autoantibodies in HTLV-1-infected patients with KCS, which suggests that other mechanisms may be involved in the pathogenesis of this manifestation. Additionally, PVL may be a marker of KCS development in these patients.