[Establishment and identification of a C57B/6 mouse sarcoidosis granuloma model].

OBJECTIVE: To establish a C57BL/6 mouse sarcoidosis granuloma model elicited by mycobacterial superoxide dismutase A peptide (SodA). METHODS: Thirty female C57BL/6 mice were randomly divided equally into 5 groups: a combination (SodA+Sepharose) group, a SodA group, a IFA (incomplete Freund's adjuvant) group, a sepharose group and a blank control group. On the first day, the combination group and the SodA group were sensitized by subcutaneous injection of 50 µg SodA incorporated into IFA 0.25 ml. The IFA group and the Sepharose group were treated with subcutaneous injection of IFA 0.25 ml and PBS 0.25 ml respectively, while the blank control group was not given any treatment. On the 14th day, the combination group was challenged by tail vein injection of 50 µg SodA covalently coupled to 6000 agarose 4B beads (in PBS 0.5 ml) . The SodA group was challenged by tail-vein injection of 50 µg SodA (in PBS 0.5 ml) . The IFA group and the Sepharose group were treated by tail-vein injection of 6000 agarose 4B beads (in PBS 0.5 ml) , while the blank control group was not given any treatment. On the 22th day, the mice were dissected and the gross and pathological changes of lymph nodes and lungs were observed. Immunohistochemisty was used to identify Mac-2 and CD(+)4T in granuloma. Counts and differentials of BALF cells were measured. CD(+)4/CD(+)8 in BALF and cytokines (IFN-γ and IL-12 ) levels in the lungs were detected by flow cytometry. RESULTS: Enlargement of peripheral and pulmonary hilar lymph nodes were found in the combination group and the SodA group, and sarcoidosis granuloma was found in the lymph nodes and lungs of the combination group. Sarcoidosis granuloma was also found in the lymph nodes but not in the lungs of the SodA group. No sarcoidosis granuloma was observed in the lungs and lymph nodes of the IFA group, the Sepharose group and the blank control group. Macrophage specific antigen Mac-2 and CD(+)4T were positive in the core and rim of the granuloma respectively. The lymphocyte percentages in the BALF of the combination group and the SodA group [(19.4 ± 6.5)% and (22.3 ± 8.5)%] were significantly higher than that in the IFA group, the Sepharose group and the blank control group [(8.5 ± 4.3)%, (7.7 ± 3.4)%, (0.8 ± 0.6%)] (P < 0.05 ). CD(+)4/CD(+)8 in the BALF of the combination group and the SodA group (3.5 ± 1.4, 3.2 ± 1.1) were significantly higher than that in the IFA group and the Sepharose group (1.2 ± 0.5, 1.0 ± 0.4) (P < 0.05 ). IFN-γ and IL-12 in the lungs of the combination group and the SodA group [IFN-γ:(32.9 ± 9.7) ng/L, (26.4 ± 7.2) ng/L; IL-12: (29.6 ± 9.4) ng/L, (26.1 ± 8.9) ng/L]were significantly higher than those of the IFA group, the Sepharose group and the blank control group [IFN-γ: (16.5 ± 6.8) ng/L, (12.2 ± 5.0) ng/L, (9.0 ± 2.6) ng/L; IL-12: (16.7 ± 4.6) ng/L, (13.6 ± 4.4) ng/L, (9.6 ± 5.3) ng/L] (P < 0.05 ). But these indexes were not significantly different between the combination group and the SodA group, and among the IFA group, the Sepharose group and the blank control group (P > 0.05). CONCLUSION: SodA can elicit sarcoidosis granuloma in C57BL/6 mice, and the immunological features of the model were similar to those in human sarcoidosis.

Sarcoidose pulmonar: uma atualização / Pulmonary sarcoidosis: an update

Na Medicina, como em muitas áreas da ocupação humana, o oculto tende a encantar. Talvez isso explique, em parte, o grande interesse em torno da sarcoidose, uma doença repleta de incógnitas e desafios ao seu entendimento. Esta revisão teve como objetivo apresentar os principais avanços no entendimento da imunopatogenia, diagnóstico e tratamento da sarcoidose pulmonar. Vários estudos têm enfatizado a importância do alelo DRB1*03 do antígeno leucocitário humano e da exposição ambiental na patogenia da doença. No tocante ao diagnóstico, o ultrassom endoscópico transesofágico, o ultrassom endobrônquico e a tomografia por emissão de pósitrons com 18F fluordesoxiglicose têm sido apresentados como exames promissores, inclusive na avaliação da resposta ao tratamento. Várias recomendações baseadas em evidências têm sugerido o uso de imunobiológicos nos casos de resistência aos corticosteroides, especialmente na sarcoidose refratária ao tratamento. O melhor entendimento da relação entre sarcoidose e exposição ambiental pode auxiliar na diferenciação dos vários fenótipos da doença. É possível que uma abordagem diagnóstica e terapêutica distinta possa ser utilizada em um futuro próximo, com base nesses fenótipos.

Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety.

BACKGROUND: Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. OBJECTIVES: To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. PATIENTS/METHODS: Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. RESULTS: Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty-four-hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin-converting enzyme correlated negatively with antibody response against B antigen (CC = -0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = -0·377, P = 0·035). No major adverse events or disease flare-up was observed during follow-up. CONCLUSIONS: In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs. Studies with larger sample size and a broader selection of subjects could help validate the results of this study.

Development of a sarcoidosis murine lung granuloma model using Mycobacterium superoxide dismutase A peptide.

Sarcoidosis is characterized by noncaseating granulomas containing CD4(+) T cells with a Th1 immunophenotype. Although the causative antigens remain unknown, independent studies noted molecular and immunologic evidence of mycobacterial virulence factors in sarcoidosis specimens. A major limiting factor in discovering new insights into the pathogenesis of sarcoidosis is the lack of an animal model. Using a distinct superoxide dismutase A peptide (sodA) associated with sarcoidosis granulomas, we developed a pulmonary model of sarcoidosis granulomatous inflammation. Mice were sensitized by a subcutaneous injection of sodA, incorporated in incomplete Freund's adjuvant (IFA). Control subjects consisted of mice with no sensitization (ConNS), sensitized with IFA only (ConIFA), or with Schistosoma mansoni eggs. Fourteen days later, sensitized mice were challenged by tail-vein injection of naked beads, covalently coupled to sodA peptides or to schistosome egg antigens (SEA). Histologic analysis revealed hilar lymphadenopathy and noncaseating granulomas in the lungs of sodA-treated or SEA-treated mice. Flow cytometry of bronchoalveolar lavage (BAL) demonstrated CD4(+) T-cell responses against sodA peptide in the sodA-sensitized mice only. Cytometric bead analysis revealed significant differences in IL-2 and IFN-γ secretion in the BAL fluid of sodA-treated mice, compared with mice that received SEA or naked beads (P = 0.008, Wilcoxon rank sum test). ConNS and ConIFA mice demonstrated no significant formation of granuloma, and no Th1 immunophenotype. The use of microbial peptides distinct for sarcoidosis reveals a histologic and immunologic profile in the murine model that correlates well with those profiles noted in human sarcoidosis, providing the framework to investigate the molecular basis for the progression or resolution of sarcoidosis.

[Likopid in the complex immunomodulating treatment of patients with sarcoidosis of the lung and intrathoracic lymph nodes]. / Likopid v kompleksnom immunokorrigiruiushchem lechenii bol'nykh sarkoidozom legkikh i vnutrigrudnykh limfaticheskikh uzlov.

AIM: To examine the functional status of the immune system in patients with lung and intrathoracic lymph nodes sarcoidosis and to evaluate the efficiency of immunomodulation alone and in its inclusion in combined treatment of the disease. MATERIALS AND METHODS: 58 patients with the disease of varying severity were followed up. Comprehensive examination, involving clinical, immunological, X-ray, and physical studies, in patients treated with combined immunotherapy was performed. Initial examination revealed mixed immunodefficiency with impaired T- and phagocytic activity. According to the degree of immunological changes, the patients were given immunotherapy, including polyoxidonium, T-activin (or immunophan) injections, a complex of multivitamins and trace elements, and total adaptogens. After partial or complete normalization of an immunogram, all the patients received licopid (two-three 10-day courses, 10 mg/day). RESULTS: The optimal result (as long as 3-year remission) was achieved in the first time diagnosed sarcoidosis who have not taken glucocorticoidal hormones. CONCLUSION: The follow-up shows that addition of licopid is a compulsory component of immunotherapy in this disease; the efficiency of treatment is determined by its multimodality. The courses of therapy should be repeated when immunological indices deteriorated.