Israel Medical Association Journal

Background: Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN[1] is characterized by neutrophil count < 500 ml and a benign self-limiting course. Detecting specific antibodies against the polymorphic human neutrophil antigen usually confirms the diagnosis. Current available tests, however, are expensive and inapplicable in many laboratories as they require the use of isolated and fixed granulocytes obtained from donors pretyped for their distinct HNA[2] alloform.

Objectives: To assess the performance of a modified test to identify by FACS-analysis granulocyte-specific antibodies in the sera of neutropenic children.

Methods: We evaluated 120 children with a clinical suspicion of AIN, whose sera were analyzed by flow cytometry for the presence of autoantibodies using the indirect granulocyte immunofluorescence test. In contrast to the traditional tests, the sera were tested against randomly selected untyped neutrophils derived from a batch of 10 anonymous healthy subjects, presumably including the common HNA alloforms. Control sera samples were from patients with chemotherapy-induced, familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded.

Results: Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods.

Conclusions: The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective aiding tool for clinical decision making.

Approximately 1 in 31 people suffers from an autoimmune disease. The clinical care of patients with autoimmunity crosses multiple disciplines within pediatrics and internal medicine, including, for example, allergy-clinical immunology, rheumatology, nephrology, hematology, pulmonology and neurology. There are two major areas that are considered in the analysis of autoimmunity in human patients. The first of course is etiology and the second, and of even greater importance, is therapy. Towards that end, considerable attention has focused on the role of hematopoietic stem cell transplantation to either reverse or modulate autoimmune disease. Indeed, it is a field that has far more promise than premise based on a variety of issues, including economics, health care delivery, and obviously efficacy and safety. To put this in perspective, we have attempted to review some of the issues that pertain to this novel approach to the management of autoimmunity. Finally, we emphasize the need to incorporate basic research into therapeutic trials, a vacuum all too often present in clinical intervention.

Experimental and clinical data suggest a causal relationship between immunological and inflammatory processes and heart failure. Inflammatory processes may be involved in the pathogenesis of heart failure and may play a role in the progression of ventricular dysfunction. In the last decade several immunological methods were developed that tried to address these questions and overcome the inflammatory and immunological insults. We hope that the present review will increase awareness of new treatment options and encourage researchers and physicians to investigate this novel approach to treat patients with heart failure.
 

Background: West Nile virus, the etiologic agent of West Nile fever, is an emerging mosquito-borne disease. WNV[1] was recognized as a cause of severe human meningo-encephalitis in elderly patients during outbreaks in various parts of the world.

Objectives: To analyze WNV encephalitis therapy and its outcome after prescribing hyperimmune gammaglobulin therapy.

Methods: Eight subjects with WNV encephalitis were treated with supportive therapy and 5 days of IVIG[2] 0.4 g/kg/day containing high WNV antibodies obtained from healthy blood donors.

Results: Patients who were treated with IVIG as soon as possible exhibited an improvement in their symptoms. All subjects presented with high fever, progressive confusion and headaches, nausea and vomining. The Glasgow Coma Screen for six patients ranged between 8 and 13 and all were discharged with a score of 15. The remaining two subjects died during their hospitalization.

Conclusions: In severe WNV infection, where the disease affects the central and/or peripheral nervous system, early intervention with IVIG together with supportive treatment is recommended.

Background Drug-specific CD8+ TH1 lymphocytes have been found in the peripheral blood and involved skin of patients with drug-induced bullous exanthems.

Objectives To determine whether the interferon-gamma release test can identify culprit drugs in pemphigus patients.

Methods Clinical and laboratory workup for pemphigus was performed in 14 pemphigus vulgaris patients who had been exposed to drugs, and the IFNl[1] release test was conducted on their lymphocytes from heparinized venous blood cultured with medium, phytohemagglutinin and one of 32 drugs, or medium and phytohemagglutinin alone.

Results Ten of the patients and 13 of the 32 drugs exhibited a positive response to the test. Eight of the 10 patients with positive IFNl test results had a less severe course of the disease, with fast reduction in steroid dosage.

Conclusions The findings demonstrate both the ability of the IFNl release test to identify drugs that can induce pemphigus, and its usefulness in the diagnostic workup of pemphigus patients.

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.

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.