Gender Bias in Human Systemic Lupus Erythematosus: A Problem of Steroid Receptor Action?

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease resulting from abnormal interactions between T and B cells. The acquisition of SLE is linked to genetic susceptibility, and diverse environmental agents can trigger disease onset in genetically susceptible individuals. However, the strongest risk factor for developing SLE is being female (9:1 female to male ratio).

Estradiol targets T cell signaling pathways in human systemic lupus.

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification.

Efficacy of intravenous gammaglobulin for immunoglobulin G subclass and/or antibody deficiency in adults.

Background: The clinical significance and efficacy of treating patients who have immunoglobulin (Ig) G subclass deficiency and/or antibody deficiency with Ig-replacement therapy has been debated. There are no clear guidelines to recommend intravenous gammaglobulin (IgIV) in these patients as there are few published studies documenting its efficacy.

Methods: We studied in an open-label protocol 10 adult patients with recurrent respiratory infections and IgG subclass and/or antibody deficiency.

Fulvestrant (Faslodex), an estrogen selective receptor downregulator, in therapy of women with systemic lupus erythematosus. clinical, serologic, bone density, and T cell activation marker studies: a double-blind placebo-controlled trial.

Objective: Estrogen plays a role in the activation of systemic lupus erythematosus (SLE) and in upregulating intracellular signals by binding to the estrogen receptor(s). Fulvestrant (Faslodex, AstraZeneca Pharmaceuticals, Wilmington, DE, USA), an estrogen selective receptor downregulator, competes for receptor binding in vitro and inhibits estrogen action in target cells. We evaluated the efficacy, side effects, and expression of T cell activation markers, following the administration of fulvestrant or placebo to premenopausal patients with SLE.

Autoimmune lymphoproliferative syndrome in a patient with common variable immunodeficiency: dichotomy of apoptosis.

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder usually associated with hypergammaglobulinemia and defective apoptosis mostly due to Fas or Fas ligand mutation. Common variable immunodeficiency (CVID) is a disorder with hypogammaglobulinemia commonly associated with increased Fas expression and spontaneous apoptosis.

Objective: To describe a patient with a unique combination of hypogammaglobulinemia and ALPS with Fas deficiency but high spontaneous apoptosis.

Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) associated with hypogammaglobulinemia and elevated serum tumor necrosis factor-alpha levels.

Pyogenic aseptic arthritis, pyoderma gangrenosum, and cystic acne (PAPA) syndrome is an unusual triad that was recently mapped to a chromosome 15q mutation. We describe a patient from this kindred in whom hypogammaglobulinemia and elevated tumor necrosis factor-alpha serum levels were detected. The patient responded well to intravenous gammaglobulin and intra-articular corticosteroid therapy.

Differential expression of estrogen receptors in women with systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease primarily affecting women. T cell activation markers (calcineurin, CD154) increase in SLE T cells cultured with estradiol 17-beta. Biological effects of estradiol are mediated through 2 receptor proteins, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta).

Increased estrogen-dependent expression of calcineurin in female SLE T cells is regulated by multiple mechanisms.

Objective: Calcineurin is a key mediator of T cell activation. Previous studies in our laboratory showed a dose-dependent and hormone-specific increase in calcineurin expression in the T cells from females with systemic lupus erythematosus (SLE). This study investigates whether the estrogen-dependent increase in calcineurin expression is due to stabilization of the messenger RNA (mRNA).

Wegener's granulomatosis: survey of 701 patients in North America. Changes in outcome in the 1990s.

Objective: To study the medical and socioeconomic impact of Wegener's granulomatosis (WG) in a large cohort (n = 701) of patients who are members of the international WG Support Group (WGSG).

Methods: Forty questions designed and validated by one of the authors and reviewed by the medical consultants of the WGSG International were mailed to 1690 patients with WG who are members of the WGSG; 701 (41%) patients returned the questions. Diagnosis of WG was self-reported for purpose of this questionnaire.

Vasculitis.

Progress has been made in the classification, characterization, and identification of vasculitis; a heterogeneous disease with various vessel sizes and types of involvement. Understanding pathogenetic mechanisms and the kinetics of the inflammatory-immune response is still in its infancy. With the availability of new tools for diagnosis and the use of molecular biological techniques at the cellular, tissue, and fluid phase levels will open the doors for new understanding of the etiology and mechanism(s) of this group of diseases.