concanavalin-a and Myositis

We studied an alpha-1-acid glycoprotein (AGP) and an alpha-1-antichymotrypsin (ACHT) microheterogeneity in sera of patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA/PMR), polymyositis/dermatomyositis (PM/DM) and healthy individuals by affinity electrophoresis with concanavalin A (Con-A) as the ligand. Our results are expressed as reactivity coefficients. The mean of AGP reactivity coefficients (AG-RC +/- SD) in PMR (0.92 +/- 0.17) and GCA/PMR (0.91 +/- 0.12) were significantly lower compared with the mean AG-RC in patients with PM/DM (1.48 +/- 0.52) as well as in healthy individuals (1.34 +/- 0.9). Moreover, an additional microheterogeneous form of AGP was noted in patients with PM/DM. In parallel, we also found that the mean of ACHT reactivity coefficients (AC-RC +/- SD) were lower in patients with PMR (2.94 +/- 1.24) and GCA/PMR (1.66 +/- 0.16) compared with healthy individuals (3.92 +/- 1.17). The mean of AC-RC in patients with PM/DM (6.74 +/- 4.35) was significantly higher than in patients with PMR and GCA/PMR as well as in healthy individuals. Our results show that the changes in reactivity of AGP and ACHT with Con-A are useful diagnostic markers for the differentiation of PMR and GCA/PMR from PM/DM.

Topics: Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antichymotrypsin; C-Reactive Protein; Child; Child, Preschool; Concanavalin A; Dermatomyositis; Diagnosis, Differential; Electrophoresis; Female; Giant Cell Arteritis; Humans; Male; Middle Aged; Myositis; Orosomucoid; Polymyalgia Rheumatica

Alzheimer amyloid precursor proteins (APP) are actively secreted by stimulated human peripheral mononuclear blood leucocytes (PMBLs). Induction of APP transcription, translation and secretion was observed with several T cell mitogens but was highest with phytohemagglutinin. The time course of induction is similar to that reported for IL-2 and IL-2 receptor. We suggest that APP may play an important role in the construction of the immunological network and the differentiation of T cells.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Concanavalin A; Gene Expression; Humans; In Vitro Techniques; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes; Myositis; Phytohemagglutinins; Pokeweed Mitogens; Protein Precursors; RNA, Messenger

The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. The nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of preirradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studies of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoimmune Diseases; Cell Division; Cell Nucleus; Concanavalin A; DNA; DNA Repair; Humans; Lupus Erythematosus, Systemic; Lymphocytes; Middle Aged; Myositis; Radiation Tolerance

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disorder of unknown aetiology. In order to study whether immunoregulatory abnormalities might be involved in this autoimmune state, we investigated the autologous mixed lymphocyte reaction (AMLR) and concanavalin A-induced suppressor cell function (Con A-induced suppression) in adult patients with primary PM/DM. We found the AMLR to be significantly depressed in patients; responsiveness could not be enhanced by increasing the numbers of non-T stimulator cells in culture, nor by varying the day on which cultures were harvested. Con A-induced suppression of T cell proliferative responses to mitogenic stimuli was normal. These findings implicate abnormal immunoregulation in the pathophysiology of PM/DM. Further, the dissociation of AMLR reactivity from Con A-inducible suppression suggests that events important for immunoregulatory competence may occur in the AMLR culture, despite the absence of an observed proliferative response.

Topics: Adult; Aged; Autoimmune Diseases; Concanavalin A; Dermatomyositis; Dose-Response Relationship, Immunologic; Humans; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Middle Aged; Myositis; T-Lymphocytes, Regulatory