Editorial

Autoimmunity and sex revisited

Based on the analysis of literature and our own data, some key concepts of natural autoimmunity are reviewed from the point of the Pathophysiology: immunological regulation of homeodynamics, physiological autoimmunity versus autoallergy and predictive roles of natural autoantibodies are discussed. Hypothesis of Immunculus and principle of Immunacea are correlated to some of clinical examples with immunopathological data and the perspectives of autoimmunomics are described.

Estrogen profoundly affects onset and severity of many immune-mediated diseases. In our murine model of drug-induced autoimmunity, female-specific, estrogen-dependent increase in splenic lymphocyte homing was directly implicated in increased disease severity. The present study evaluated the effect of estradiol on microvascular endothelial cells from the spleen compared to endothelial cells from the dermis, which has no disease manifestation in this model. Estradiol increased spleen endothelial cell estrogen receptor (ER) alpha 2.9-fold and decreased estrogen receptor beta 2.1-fold while decreasing both receptors on dermal cells. Estradiol enhanced adhesion of D10 cells to spleen but not dermal endothelial cells 1.53-fold (P < 0.001), an increase that was inhibited by antibodies to VCAM-1 and ICAM-1, and by the estrogen receptor antagonists tamoxifen and ICI 182,780. Estradiol induced greater VCAM-1 expression on spleen than dermal endothelial cells (P < 0.05). Estradiol increased spleen endothelial cell estrogen receptor alpha 2.9-fold and decreased estrogen receptor beta 2.1-fold while decreasing both receptors on the dermal cells. Estrogen specifically and preferentially promoted spleen chemokine protein expression for MCP-1 and MCP-3, while having no effect on dermal protein expression for these chemokines. Estradiol-mediated effects on splenic chemokines were abrogated by tamoxifen and ICI 182,780. The gender-specific increase in lymphocyte homing to spleen may be attributable, at least in part, to tissue-specific estrogen-mediated effects on microvascular endothelial cells.

Objective: To describe a possible role for estrogen in the induction or acceleration of Sjögren's syndrome (SS). Method: Two healthy young women who received estrogen-increasing therapy and then developed full-blown SS are described. The relationship between SS and estrogen therapy is discussed and the available literature reviewed. Results: Both women developed SS 3 years after starting estrogen-increasing treatment. The syndrome was severe in the first patient, who was treated with a high dosage of estrogen; the disease was moderate in the second patient, who received a lower estrogen dosage. Conclusion: Estrogen may play a role in the pathogenesis of SS in some patients. Semin Arthritis Rheum 30:209-214. Copyright © 2000 by W.B. Saunders Company

Pregnancy is a unique immunologic state where a natural homeostasis exists between antigenically different tissues. Several earlier studies have addressed the fluctuations in the number and/or function of lymphocytes, including B cells during pregnancy, but changes within the subsets of B lymphocytes, conventional (CD5⁻) and B-1 (CD5⁺), have not been addressed. Here we demonstrate that the frequency of B-1 cells decreases dramatically during pregnancy, whereas the frequency of conventional B cells remains relatively constant. The missing B-1 cells return to pre-pregnancy levels 8–10 weeks after parturition. The polyreactive autoantibodies secreted by B-1 cells have been implicated in autoimmunity and immune regulation. The possible role of B-1 cells during pregnancy will be discussed in that context.

The effect of thyroxine (T₄) and recombinant (rcGH) or purified pituitary-derived (pcGH) chicken growth hormone on the development of spontaneous autoimmune thyroiditis (SAT) was examined in the Obese strain (OS) chicken. Day-old OS chicks were randomly assigned to a control or 1.0 ppm T₄ supplemented diet and a vehicle or 500 μg rcGH/kg BW daily injection, using a 2×2 factorial design. At 4 weeks, sera were analyzed for anti-thyroglobulin autoantibody (TgAAb) using a kinetics-based ELISA. Leucocytic infiltration of the thyroid was assessed using computer-based video imaging techniques. A close correlation between TgAAb and thyroid infiltration was seen with both being decreased (p<0.05) by the T₄/rcGH treatment. Neither the T₄ or rcGH alone produced this effect and the rcGH treatment significantly elevated TgAAb. In a second experiment, all but the control group received 1.0 ppm T₄ supplementation and two of the T₄-treated groups received either 50 or 200 μg pcGH/kg BW by daily injection. As before, T₄/pcGH significantly reduced TgAAb and thyroid infiltration. T₄ alone produced no significant effects. These data support the conclusion that the combined treatment of T₄ and cGH exert an immunomodulatory effect within a strain that is predisposed to autoimmune thyroiditis while GH treatment alone exacerbated the condition. These results also show that video imaging techniques can be used to evaluate the extent of histopathology present within the OS thyroid.

Low doses of HgCl₂ induce a genetically restricted autoimmune syndrome in Brown Norway (BN) rats (BN(Hg)). Part of the syndrome iucludes spontaneously developing mononuclear cell foci in salivary and lacrimal glands, morphologically similar to focal sialoadenitis in Sjögren's syndrome in man. In this study, we have shown that Hg-induced focal adenitis in BN rat is not female predominant and not solely dependent on Hg uptake in the glands. In BN(Hg), focal adenitis was found to develop in several different glands (parotid, submandibular, lacrimal, thyroid) as a specific manifestation of immunopathosis induced by Hg in the RT1ⁿ-haplotype-carrying BN. Such manifestations were absent in another strain, the Hg-resistant Lewis (RT1ⁿ). Also a patent contact sensitizer, DNFB, induced focal adenitis in isolated glands, provided that strong sensitization had occurred. Immunohistochemical characterization of focal adenitis in BN(Hg) with monoclonal antibodies showed that T cells and dendritic cells dominate the early infiltrates, whereas B cells were absent.