Autoimmunity and Novel Therapies in Immune-Mediated Thrombocytopenia

Immune-mediated thrombocytopenic purpura (ITP) is recognized as a cell-specific autoimmune disorder, yet, multifactorial in origin. The development of thrombocytopenia is well proven to be mediated by both humoral (anti-platelet antibodies) and cellular (T-cell) mediated mechanisms. In some cases other autoantibodies are also induced, eg, antinuclear antibody (ANA), anti-dsDNA, and anti-cardiolipin, in addition to anti-platelet antibodies. The persistance of these autoantibodies during the course of ITP could herald future development of another autoimmune disease, eg, systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). Due to the better understanding of the pathophysiology of ITP, new novel therapies were introduced aiming to achieve long-lasting remissions. In this review we will focus on the autoimmune nature of the disease and on some of the mechanisms of action of these new therapies

New Biological Treatment Options in CSU

Chronic spontaneous urticaria (CSU) is a devastating disease and is associated with many co-morbidities and long-lasting suffering. Therefore, patients always look for a most efficient therapeutic approach to achieve a full remission. In many patients, CSU remain refractory to off-label doses of antihistamines and short courses of steroids, and therefore are treated with omalizumab. However, 15–20% of severe CSU patients will stay unresponsive to omalizumab and are defined as being of un-met needs. In this review we will shed light on the many new drugs which are assessed in ongoing clinical trials

Semaphorin 3A Is Effective in Reducing Both Inflammation and Angiogenesis in a Mouse Model of Bronchial Asthma

Semaphorin 3A (sema3A) belongs to the sub-family of the immune semaphorins that function as regulators of immune-mediated inflammation. Sema3A is a membrane associated molecule on T regulatory cells and on B regulatory cells. Being transiently ligated to the cell surface of these cells it is suggested to be a useful marker for evaluating their functional status. In earlier studies, we found that reduced sema3A concentration in the serum of asthma patients as well as reduced expression by Treg cells correlates with asthma disease severity. Stimulation of Treg cells with recombinant sema3A induced a significant increase in FoxP3 and IL-10 expression. To find out if sema3A can be of benefit to asthma patients, we evaluated the effect of sema3A injection in a mouse model of asthma. BALB\c-mice were sensitized using ovalbumin (OVA) + adjuvant for 15 days followed by OVA aerosol inhalation over five consecutive days. Four hours following air ways sensitization on each of the above days- 15 of these mice were injected intraperitoneally with 50 μg per mouse of recombinant human sema3A-FR and the remaining 15 mice were injected with a similarly purified vehicle. Five days later the mice were sacrificed, broncheo-alveolar lavage (BAL) was collected and formalin-fixed lung biopsies taken and analyzed. In sema3A treated mice, only 20% of the bronchioles and arterioles were infiltrated by inflammatory cells as compared to 90% in the control group (p = 0.0079). In addition, eosinophil infiltration was also significantly increased in the control group as compared with the sema3A treated mice. In sema3A treated mice we noticed only a small number of mononuclear and neutrophil cells in the BAL while in the control mice, the BAL was enriched with mononuclear and neutrophil cells. Finally, in the control mice, angiogenesis was significantly increased in comparison with sema3A treated mice as evidenced by the reduced concentration of microvessels in the lungs of sema3A treated mice. To conclude, we find that in this asthma model, sema3A functions as a potent suppressor of asthma related inflammation that has the potential to be further developed as a new therapeutic for the treatment of asthma

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

Diagnosis and treatment of urticaria and angioedema: a worldwide perspective

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide

Antiviral Treatment Down-Regulates Peripheral B-Cell CD81 Expression and CD5 Expansion in Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5(+) subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5(+) B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5(+) B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5(+) population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5(+) peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation