IMMUNOLOGY OF SARCOIDOSIS
Section snippets
IN VITRO STUDIES OF PERIPHERAL BLOOD LYMPHOCYTES
The early studies on lymphocytes were directed toward defining the mechanism of cutaneous anergy in sarcoidosis. Interestingly, those studies proved to elucidate the immunopathogenesis of sarcoidosis. The studies performed on peripheral blood lymphocytes in sarcoidosis fall into four groups—(1) proliferative responses of lymphocytes to stimulation with mitogens and recall antigens; (2) lymphocyte proliferation in mixed lymphocyte cultures; (3) spontaneous lymphoblastic transformation and
PHYTOHEMAGGLUTININ SKIN TEST
As with various recall antigens, mitogens such as PHA and concanavalin-A also activate peripheral blood T lymphocytes and cause them to release soluble lymphokines, which then attract monocytes to the site injected with antigen or mitogen. The PHA skin test has been used to explore the state of cellular immunity in a variety of disorders. Defective in vivo response has been found in lymphoproliferative diseases162 or with congenital defects of cellular immunity, including thymic dysplasia,
Hypergammaglobulinemia
Polyclonal hypergammaglobulinemia is common in sarcoidosis. We reported elevated levels of serum immunoglobulin G (IgG) and IgM in 7 of 14 untreated patients. One of the patients also had elevated serum IgA levels.76 In 10 treated patients, hypergammaglobulinemia was less frequent: IgG and IgM were each elevated in only one patient and IgA was elevated in two patients. Subsequently, we extended our observations to 211 patients and found that 68% (81% of blacks and 55% of whites) had
CELLULAR IMMUNITY AND THE MECHANISM OF SARCOID GRANULOMA FORMATION
The mechanisms of hypersensitivity granuloma formation by infectious (e.g., tuberculosis) and noninfectious (e.g., berylliosis) agents have striking similarities and provide a framework for comparative analysis with the immunopathology of sarcoidosis. Insights into the mechanisms come from studies of peripheral blood, BAL, and in vitro-cultured intact sarcoidal skin granulomas.75 Fiberoptic bronchoscopy revolutionized the clinical diagnosis and research of sarcoidosis because it provided a
CUTANEOUS ANERGY
In Boeck's time, a cutaneous response to tuberculin was commonplace in the general population.7 Negative tuberculin reactions in sarcoidosis patients did not imply absence of prior tuberculous infection.51 Indeed, the observation that the finding was caused by suppression of previously existing tuberculin sensitivity was based on direct observations in patients with known positive tuberculin reactions prior to the onset of sarcoidosis.51 Evidence of previous tuberculous infection was also
ROLE OF IMMUNOLOGY IN DEFINING THE CAUSES OF SARCOIDOSIS
The previously described hypothetical model of granuloma immunopathogenesis in sarcoidosis is based on extensive, albeit indirect, evidence that antigen presentation is the initiating stimulus for granuloma formation. A nagging question is whether the resultant hyperactive cellular arm of the immune system in sarcoidosis is the result of a specific antigenic stimulus or the result of a nonspecific polyclonal phenomenon, analogous to the hypergammaglobulinemia of the humoral arm. Investigation
FUTURE DIRECTIONS
The demonstration of granulomagenic activity in autologous sarcoid alveolar macrophages and monocytes serves as a beacon for further pursuit of the initiating antigenic events of sarcoid granuloma formation. Because of its association with lysosomes and cell membranes, it is likely that the granulomagenic factor is a ligand of MHC-class 2 molecules, providing an opportunity for its isolation by monoclonal immunopurification of those molecules. Once isolated, the antigen could be further studied
SUMMARY
Because of its association with cutaneous anergy, sarcoidosis was originally viewed as a defect of cellular immunity. Supporting that misperception were early studies of peripheral blood lymphocytes that found lymphopenia and impaired lymphocyte responses to mitogens and recall antigens. The clue to a vast underlying network of complex hyperactive cellular immune functions was discovered in the paradoxical finding of in vitro spontaneous lymphoblastic transformation and lymphokine production.
ACKNOWLEDGMENT
The authors thank Nick Shukla and Wei Li for their dedicated technical assistance, and H. Kim Park for her expertise in dermatopathology.
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Cited by (0)
Address reprint requests to Yash P. Kataria, MD Section of Pulmonary and Critical Care Medicine Department of Medicine East Carolina University School of Medicine 3 East 149 Brody Building Greenville, NC 27858
This work was supported by grants from the American Lung Association of North Carolina.