Israel Medical Association Journal

Neonatal lupus erythematosus is an uncommon transplacentally Acquired Autoimmune Disorder. The most common clinical manifestations are skin rash, congenital atrioventricular block, thrombocytopenia, leucopenia, anemia, and hepatosplenomegaly. Usually, the skin rash resembles subacute cutaneous lupus, but different forms of rash have been reported in Neonatal lupus erythematosus and some are rare forms. NLE should be suspected in babies with atypical skin lesions, even if present at birth.  

High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1[1] can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 gets tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA[2], HMGB1 appears to be crucially involved in the pathogenesis of arthritis, since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.

Idiotypic analyses of anti-DNA autoantibodies were widely reported a decade ago. More than 100 studies were conducted on one of the main analyzed idiotypes, the 16/6 Id of the anti-ssDNA monoclonal antibody. In this review we summarize current knowledge on the characteristics of the 16/6 Id[1], its link to infection and its target epitopes on other molecules known so far. This includes the modulation of T and B cell responses and gene expression by the 16/6 mAb[2] in vitro and in vivo. We focus on the ability and mechanisms by which this idiotype induces experimental lupus in naïve mice, manifested by autoantibody spread, kidney and brain involvement, and leukopenia associated with enhanced sedimentation rate. We also discuss various therapeutic modalities to treat 16/6 induced lupus in mice.

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.