Abnormal Structures in Circulating Lymphocytes from Patients with Systemic Lupus Erythematosus and Related Diseases

Abstract

A prospective electron microscopic study, incorporating blind controls, demonstrated tubuloreticular structures (TRS) in the buffy coat lymphocytes of 32 patients with connective tissue disease. From 1 to 8% of the lymphocyte sections were involved. The abnormal structures consisted of interwoven, electron-dense tubules (220 to 280 A diameter) which were located within the endoplasmic reticulum. Tubuloreticular structures were found in lymphocytes from 20 of 30 patients with systemic lupus erythematosus (SLE), 2 of 4 with discoid lupus erythematosus, 8 of 20 with other connective tissue disease and none of 22 control cases. Clinical evaluation of the patients with SLE disclosed no specific differences between those with TRS-positive or TRS-negative lymphocytes; there were some indications of greater disease activity in the TRS-positive group. The biologic nature of TRS is unknown, but they have been linked to virus infection under both clinical and experimental conditions. systemic lupus erythematosus (SLE) (3-6) and many patients with related diseases of connective tissues (7-9). We now report a significant frequency of morphologically identical structures in the circulating lymphocytes of such patients.T h e tubules in question have been distinguished by their ultrastructural appearance. They are relatively electron-dense and measure in the range of 220 to 280 A in diameter. They are interwoven within membrane-limited compartments which can often be identified as dilatations of the endoplasmic reticulum or perinuclear space. T h e biologic nature of these structures is still unknown, and we have adopted the description tu buloreticular struclures (TRS) also proposed by Dalton (1 0).T h e possibility of finding T R S in circulating cells was suggested by electron microscopic examination of a skin biopsy from a 24-year-old man with SLE with subcutaneous nodules and histologic evidence of chronic vasculitis. Thin

Tubular structures in endothelium in palindromic rheumatism

“…Despite the accumulating evidence that tubuloreticular structures are not disease specific, their presence in capillary endothelial cells or circulating mononuclear cells is certainly an integral feature of the multisystem connective tissue diseases (2,7,8), and there are some intriguing clinicopathologic correlations which should provoke further clinical and experimental investigation. The presence of tubuloreticular structures in endothelial cells of a particular tissue has often been associated with gross or histologic alterations secondary to a disease process.…”

“…Examples include encephalitis (9), pulmonitis (lo), dermatitis (1 1) or synovitis (4), as in the present case. The involvement of lymph node (6) or circulating mononuclear cells (2,12) in SLE and other connective tissue diseases (2) has not yet been explained, but it must also reflect a pathologic alteration of the lymphoid system.…”

“…As about half the patients with palindromic rheumatism eventually develop a positive test for rheumatoid factors, and as some develop rheumatoid arthritis within a few years, many rheumatologists believe that palindromic rheumatism is an atypical form of rheumatoid arthritis (2).…”

Acute optic neuritis: A virological study in relation to multiple sclerosis

“…Moreover, they do not seem unique to MS and ON, nor do they seem to be found only in the peripheral blood mononuclear cells. Similar structures have been seen in kidney tissue, neuroglial cells, Schwann cells, fibroblasts, and cardiac muscle cells in a number of different viral infections and in several nonviral diseases (Blinzinger, Anzil, and Jellinger, 1974;Bove and Schwartz, 1973;Daniels et al, 1974;Dubois-Dalcq, Coblentz and Pleet, 1974;Faris and Martinez, 1972;Grimley, et al, 1973;Raine et al, 1975;Shaw and Sumi, 1975;Sinkovics, Gyorkey, Thoma, 1969). In the light of these considerations, we are inclined to think that the filaments are not viral structures, although we cannot exclude the possibility that the typical nuclear changes present in the leukocytes of ON and MS patients might be related to a peculiar host response mechanism to a viral infection common for ON and MS. Because we have seen the intranuclear filaments only in MS and ON patients' mononuclear cells, and not in cells from numerous healthy controls and patients with other CNS and non-CNS diseases (manuscript in preparation), we are currently extending this study to a larger patient population, which includes several additional groups of controls, in order to examine the possible relation of these filaments to the etiology of MS and ON.…”

Clinical immunologic studies in systemic lupus erythematosus

“…Thus, if SLE is related to intrinsic viral infection or viral persistence within certain tissues, it is conceivable that T cells or the general progeny of thymocytes might indeed be a fertile medium for actual expression of a putative viral agent. The numerous reports of viral or viral-like inclusions detected in renal biopsy material as well as in the case of some circulating peripheral leukocytes might be used to support such a concept (19,20). Indeed, if a viral agent were directly related to SLE, and if this agent preferred the milieu of T cells, such cells might be expected to be more likely than normal cells to eventually self-destruct and thus to result in a diminution of circulating T-cell mass.…”