Efficacy and Safety of Anti-Interleukin-20 Monoclonal Antibody in Patients With Rheumatoid Arthritis: A Randomized Phase IIa Trial.

Objective: Interleukin-20 (IL-20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109-0012, a selective anti-IL-20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy.

Methods: Sixty-seven patients with RA were enrolled and randomized (2:1) to receive NNC0109-0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double-blind, 12-week trial with a 13-week followup.

Key data elements for use in cost-utility modeling of biological treatments for rheumatoid arthritis.

Objectives: Economic evaluation is becoming more common and important as new biologic therapies for rheumatoid arthritis (RA) are developed. While much has been published about how to design cost-utility models for RA to conduct these evaluations, less has been written about the sources of data populating those models. The goal is to review the literature and to provide recommendations for future data collection efforts.

CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases.

Maintenance of immune tolerance in the periphery can be envisioned as a balance between autoreactive lymphocytes and regulatory mechanisms that counteract them. The naturally occurring CD4(+)CD25(+) regulatory T cells (T(REGs)) have a major role in modulating the activity of self-reactive cells. The identification of Forkhead box P3 transcription factor (FoxP3) as the critical determinant of T(REG) development and function has provided new opportunities and generated expanded interest in studying the balance between autoimmunity and regulatory mechanisms in human autoimmune diseases.

Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus.

CD4(+)CD25(+) T regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance to nuclear components. We hypothesized that altered function of CD4(+)CD25(high) Tregs might play a role in the breakdown of immunologic self-tolerance in patients with SLE.

An N-linked glycan modulates the interaction between the CD1d heavy chain and beta 2-microglobulin.

Human CD1d molecules consist of a transmembrane CD1 (cluster of differentiation 1) heavy chain in association with beta(2)-microglobulin (beta(2)m). Assembly occurs in the endoplasmic reticulum (ER) and involves the initial glycan-dependent association of the free heavy chain with calreticulin and calnexin and the thiol oxidoreductase ERp57. Folding and disulfide bond formation within the heavy chain occurs prior to beta(2)m binding.

TNF downmodulates the function of human CD4+CD25hi T-regulatory cells.

CD4+CD25+ T-regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. However, little is known about the exogenous factors that regulate their differentiation and function. Here, we report that TNF inhibits the suppressive function of both naturally occurring CD4+CD25+ Tregs and TGFbeta1-induced CD4+CD25+ T-regulatory cells.

Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes.

Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick.

A pilot study of the use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography to assess the distribution of activated lymphocytes in patients with systemic lupus erythematosus.

Objective: The 2-[(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) technique provides information on uptake and metabolism of glucose in various tissues. Compared with resting cells, activated lymphocytes take up radioactively labeled glucose analog at a higher rate, which makes it possible to identify lymphoid organs with higher concentrations of activated lymphocytes. This study was undertaken to compare the pattern of PET images and quantitative FDG uptake in lymphoid organs of patients with active systemic lupus erythematosus (SLE) versus patients with inactive SLE and to correlate these findings with peripheral blood lymphocyte phenotypes.

Objective and subjective sleep disturbances in patients with systemic lupus erythematosus.

Objective: To assess objective and subjective evidence of sleep disorders in patients with systemic lupus erythematosus (SLE) and to examine correlations between parameters of lupus activity, depression, and sleep disturbances.

Methods: Fourteen SLE patients and 11 normal control subjects of similar age underwent all-night polysomnography on 3 consecutive nights. The patients and controls were also evaluated for daytime sleepiness by the Multiple Sleep Latency Test and completed a sleep disorders questionnaire and the Beck Depression Inventory.

Visceral larva migrans mimicking rheumatic diseases.

Objective: To report rheumatologic or rheumatologic-like manifestations of the visceral larva migrans (VLM) syndrome.

Methods: We carried out a prospective study of patients with VLM seen in a private practice setting in Mexico City between 1990 and 1993.

Results: From a population of 600 patients we identified 6 patients (5 women) with VLM.

Cellular and humoral immune parameters in women with pathological hyperprolactinemia before and during treatment with bromocriptine.

Problem: Experimental and clinical evidence has suggested an immunostimulatory effect of prolactin and that bromocriptine, an inhibitor of prolactin release, counteracts the actions of prolactin on the immune system. The aim of this study was to determine the impact of elevated serum prolactin levels on the immune system in patients with pathological hyperprolactinemia.

Method: For this purpose, parameters of the cellular and humoral immune system were studied in six women with prolactinomas and one with idiopathic hyperprolactinemia.

Peripheral blood lymphocyte subsets and serum immunoglobulins in Sheehan's syndrome and in normal women during the menstrual cycle.

Objective: There has been increasing evidence on the mechanisms underlying the interactions between the neuroendocrine and the immune systems, particularly in animal models with relatively few information in the human. In this study, we evaluate the cellular and humoral immunity in female patients with hypopituitarism and in normal women throughout the menstrual cycle in an attempt to determine the role of pituitary and gonadal hormones on the immune system.

Design: Serum immunoglobulins, peripheral blood lymphocyte subsets, and serum hormones were measured in eight patients with postpartum pituitary necrosis (Sheehan's syndrome) and in six normal women along different phases of the menstrual cycle, taking advantage of the lack of pituitary function and the cyclic variations in serum hormones, respectively.

Reduced dopaminergic inhibition of thyrotropin release in hyperprolactinemic ovulatory women.

It has been suggested that menstrual irregularities in hyperprolactinemia are secondary to an increase in hypothalamic dopaminergic activity via a short loop positive feedback of prolactin (PRL). We have studied this question in a relatively new syndrome characterized by hyperprolactinemia without derangements of the hypothalamic-pituitary-ovarian function due to macroprolactinemia (abnormal high amounts of big-big PRL). Central dopaminergic activity was investigated by the administration of the dopamine antagonist domperidone to normal women (n = 7) and women with anovulatory (n = 6) and ovulatory hyperprolactinemia (n = 2).

Familial occurrence of big-big prolactin as the predominant immunoreactive human prolactin species in blood.

The occurrence of big-big prolactin (PRL) as the major form of circulating immunoactive PRL has been described in ovulatory hyperprolactinemia. In this study, we have analyzed the heterogeneity of circulating human PRL in 17 members of three families in which one member, bearing galactorrhea-hyperprolactinemic syndrome, was known to have serum big-big PRL as the predominant circulating species. Gel filtration patterns of serum samples of all subjects revealed the presence of significant proportions of big-big PRL in more than one member of the same family, thus suggesting the familial occurrence of big-big as the predominant immunoreactive PRL species in blood.