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Introduction: Several factors suggest a genetic predisposition to sarcoidosis, namely the recognition of race as a risk factor and the occurrence of familial clustering of cases. Several studies have reported an association of sarcoidosis and HLA class I and especially class II alleles in different populations., Aim: HLA class I, class II and TNF-alpha genotyping in a group of sarcoidosis patients and its relation with clinical presentation and outcome., Material and Methods: A total of 104 sarcoidosis patients were included. Clinical presentation, functional, radiology, BAL findings and organ involvement were studied. HLA- A*, -B*, -C*, DRB1*, DQB1* and TNF-alpha were genotyped by molecular biology methods. DNA was extracted from peripheral blood and PCR-SSP and PCR-reverse hybridisation methods were used. Allele frequencies were compared with controls from the same region. The X2 test was used for discrete values and the Kruskal-Wallis test for continuous values., Results: When patients were compared with controls we noticed increased frequencies of B*08 (10.6% vs. 6.1%), O.R.=1.8, C.I.=[1.1;3.1], p=0.02; DRB1*12 (4.3% vs. 1.7%), O.R.=2.63, C.I.=[1.1;6.1], p=0.03. Patients with erythema nodosum have increased frequencies of the alleles DRB1*03 (28% vs. 9.3%), R.R.=2.39, C.I.=[1.5;3.8], pc=0.01 and DQB1*02 (38% vs. 18%), R.R.=2.1, C.I.=[1.3;3.3], pc=0.02. Allele DQB1*03 is decreased in patients with obstructive pattern R.R.=0.53, C.I.=[0.3;0.9], pc=0.05. Allele DRB1*15 is related to restrictive pattern and reduced diffusion capacity (21.1% vs. 6.6%), R.R.=2.46, C.I.=[1.35;4.48], p=0.01 and (18.1% vs. 3.8%), R.R.=1.87, pc= 0.05 respectively. The TNF-alpha A/A (high) genotype is significantly associated with erythema nodosum (p=0.04)., Conclusions: These data add support to the genetic association of HLA class I and II with sarcoidosis in terms of susceptibility, type of presentation, severity and outcome. Moreover as previously described in other populations, the TNF-alpha A/A (high) genotype has a significant association with erythema nodosum.

Unlabelled: Allergen-specific immunotherapy has been used for successful treatment of atopic diseases. They may act by modifying the patterns of cytokines produced by T cells. However, the precise mechanism by which it accomplishes these effects is still incompletely understood., Objective: To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients., Methods: We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period. Six of these patients were studied before and after immunotherapy. Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups. Intracellular cytokine production (IFN-g; IL-4; IL-5; IL-10) was determined by flow cytometry following stimulation with phorbol myristate acetate (PMA), ionomycin and brefeldin. Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis., Results: The expression of IL-4 and IL-5 in T cells, characteristically increased in atopic patients, respectively 13.8 (3.1 - 31.8) and 6.7% (1.0 -20.4), was significantly lower in the immunotherapy group [5.4 (2.9 -15.6) p=0.007 and 2.1% (0,6 - 4.8) p=0.035] and similar in the non-atopic control group. The levels of IFN-g did not differ between the studied groups but the ratio IFN-g / IL-4 produced by CD4+ T lymphocytes increased significantly in the patients receiving immunotherapy. In addition, there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls [1.9 (1.0 - 4.9) versus 1.4% (0.9 - 1.4) p=0.02], being more evident in CD8+ T lymphocytes. IL-10 correlated significantly with all the profile T2 cytokines (IL-4 and IL-5) and with the phenotype Tc2., Conclusion: After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production, characteristically increased in atopic disease. The increase of IL-10 that we found in our study suggested the existence of a profile T2 regulatory population, more evident in CD8+T lymphocytes.

Extrinsic Allergic Alveolitis (EAA) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles has been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of EAA seen in our practice: Suberosis and Bird Fancier's Disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8+/-11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3+/-11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of EAA had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 105 ml-1 cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-1 cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in Bird Fancier's Disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p <0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are EAA with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.