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Biomedical subjects

R I Fox

Publications and source records attributed to R I Fox.

131 records · Page 8Linked to original sources
PubMedDate not supplied

Reactivation of Epstein-Barr virus in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and destruction of salivary and lacrimal glands. This condition may be limited to glandular tissues or may be associated with other autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus. Since the environmental factors that initiate SS are unknown, we have investigated the potential role of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and other viruses. We observed that epithelial cells in salivary gland biopsies of SS patients contained antigens reactive with monoclonal antibodies against EBV-associated antigens. These antigens were not found in other tissues of SS patients and were absent in salivary gland biopsies from normals and patients with other autoimmune diseases lacking SS. Also, the content of EBV DNA in the saliva of SS patients was significantly greater than in age- and sex-matched controls or individuals with other autoimmune disorders. These studies provide one of the first examples where a specific viral agent may be implicated in perpetuating a chronic autoimmune disease. However, great caution must be used before an etiologic role can be attributed to an ubiquitous agent such as EBV.

Antibodies, Monoclonal↗
PubMedDate not supplied

Estrogen in autoimmunity: expression of estrogen receptors in thymic and autoimmune T cells.

OBJECTIVE: To identify the targets of estrogen in immune system lymphocytes and to examine gender differences in autoimmunity. DESIGN: RNA samples from purified lymphocyte subsets were analyzed for the presence of mRNA for estrogen receptor alpha and beta (ER alpha and ER beta). Groups of male, female, and testicular-feminized mice were compared for autoantibody production. SUBJECTS: Autoimmune-prone lpr (Fas-deficient), testicular-feminized (Tfm, androgen receptor-deficient) and wild-type mice were studied. METHOD: Lymphocyte subsets were purified by fluorescence-activated cell sorting (FACS) and RNA was assessed for the presence of estrogen receptor sequences using specific oligonucleotide primers and the reverse transcription-polymerase chain reaction (RT-PCR). Spontaneous and induced antibody production in mice was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ER alpha was expressed in all lymphocyte subsets examined. ER beta was expressed at low levels in thymic CD4/CD8- T cells in wild-type mice and at high levels in the peripheral CD4-/CD8- T cells in lpr mice. Both spontaneous and induced autoantibody production was higher in female lpr mice than in male lpr mice. CONCLUSIONS: The presence of ERs in lymphocytes indicates that estrogen may affect immune cells during their development and mature function. The selective expression of ER beta may help explain some of the physiological effects of estrogen and its pharmacologic analogues and may lead to means to direct estrogen analogues to such cells. Such effects may be explored in lpr mice, given the enhanced capacity of female lpr mice for autoantibody production.

Androgen-Insensitivity Syndrome↗
PubMedDate not supplied

Autoantibody production in Sjögren's syndrome: a hypothesis regarding defects in somatic diversification of germ line encoded genes.

Patients with primary Sjögren's syndrome (SS) have rheumatoid factor (anti-IgG Fc antibody, RF) in their sera that contains a crossreactive idiotype (CRI) defined by monoclonal antibody 17-109. This CRI is shared by SS patients and certain patients with Waldenstrom's macroglobulinemia. This CRI was not found in increased frequency in RF from rheumatoid arthritis patients lacking SS. The structural basis for this CRI is the highly conserved kappa chain of the Vk IIIb sub-subgroup. In SS patients, the CRI is present on both IgA RF and IgM RF, accounting for 5-20% of the total RF. Recent studies have shown that a germ line encoded kappa variable region gene (Humkv 325, cloned from a placental DNA library) has DNA sequence that encodes the variable region amino acid sequences of CRI positive kappa chains. Using MoAb 17-109, we have been able to determine the tissue distribution of CRI+ B-cells. We found an increased frequency in the salivary gland biopsies of SS patients and also in their intestinal mucosal tissues (i.e. Peyer's patch). In comparison, we also detected an increased frequency of CRI+ B-cells in the Peyer's patch regions of normals. Taken together, these results suggest that CRI+ B-cells may play an important role in normal mucosal immunity and these CRI+ B-cells have migrated to the salivary gland in SS patients as part of the inflammatory process directed at autoantigens or exogenous antigen(s) located at a mucosal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗