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Highlights of the European Society for Immunodeficiencies Meeting

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Javier Carbone, MD, PhD
Hospital Genearl Universitario Gregorio Marañon
Madrid, Spain

The 17th Biennial Meeting of the European Society for Immunodeficiencies (ESID) was held in Barcelona, Spain on 21 - 24 September 2016. Basic and clinical research in the field of primary immunodeficiencies (PID) was covered at this year's meeting from diagnostic immunology, to genetics and the immunobiology of immunodeficiency, immune dysregulation and inflammation. These topics together with other advances in the area of tolerance induction and new insights into cellular therapies were discussed through distinct keynote lectures, symposia, educational workshops and meet-the-professor sessions.

Thymic function can be determined by T-cell receptor excision circle (TREC) analysis. A perspective on newborn screening in the United States was presented by Jennifer Puck, from the Department of Pediatrics at the University of California, San Francisco School of Medicine. The TREC test for newborn screening of severe T-cell deficiencies was approved for severe combined immunodeficiencies screening by the US Food and Drug Administration (FDA) in 2014.

Targeted therapies have emerged as new treatment options for several diseases including cancer, autoimmune disorders and transplantation. Ibrutinib is a protein-tyrosine kinase inhibitor of Bruton's tyrosine kinase (Btk), a kinase of the B-cell receptor signaling pathway. Ibrutinib is FDA-approved for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma and Waldenström's macroglobulinemia. BTK-inhibitors are an example among drugs emanating from research on PID. Edvard Smith from the Karolinska Institut in Sweden, presented data on the effects ibrutinib in CLL patients including the induction of decreased levels of CCL3, CCL4 and CD16-positive 6-sulfo LacNAc (SLAN) positive monocytes.

Complement C3 hypocomplementemia is frequent after heart transplantation. Interestingly, Anais Jimenez-Reinoso from the Complutense University, Madrid, Spain, demonstrated that in vivo naïve B cell differentiation to memory B cells was selectively impaired in both primary and secondary extracellular C3 deficiency.

It is important to remember that antibody deficiency can be present in patients with normal serum IgG concentration. B. Lopez from the Lille University, France, presented data of patients with specific polysaccharide antibody deficiency, defines as an impaired antibody response to polysaccharide antigens and normal serum IgG/A/M and IgG subclass levels.

Jose Lucena from the Hospital Virgen del Rocio, Seville, Spain, reported on immunological characteristics in patients with selective IgM deficiency. Lower percentages of non-switched memory B-cells were observed in these patients.

Gain-of-function mutations refers to a mutation that confers new or enhanced activity on a protein. It has been shown recently that some primary antibody deficiencies are caused by hyperactivation of the PI3K signaling pathway, as gain-of-function mutations. Maria Martínez from the Gran Canaria Hospital, Spain, suggested that gain of function mutations in PIK3R1 can be found in patients with a narrow clinical phenotype (i.e. with only respiratory infections) suggesting that early diagnosis and careful analysis of B and T-cells followed by genetic analysis is necessary in these cases.

To establish whether hypogammaglobulinemia is due to a latent primary antibody deficiency, that becomes manifest after Rituximab therapy, or to Rituximab treatment that causes a persistent B cell defect, is a difficult task in some cases. Viviana Moschese from the Tor Vergata University, Rome, Italy, suggested the need of an extensive immunological characterization before and after Rituximab therapy.

Interindividual variations of immunoglobulin constant heavy G chain genes are identified by alternative genetic markers of IgG3, IgG1 and IgG2. They express structurally and functionally innate IgG molecules and B cells. The alternative innate IgG subclass proteins are unique entities and have different structures and functions. New individual innate IgG subclass variants were described by Vivi-Anne Oxelius from the Lund University in Sweden. The alternative IGHG subclass genes respond differently to bacterial antigens, virus and allergens, having impact on diseases and phenotypes of diseases.

A characterization of antibodies against 24 pathogens was performed by N. Marzo et al from the Bioscience Industrial Group Grifols, Barcelone, Spain, in 12 commertial intravenous immunoglobulin (IVIG) brands obtained from pooled plasma of different geographic areas. Overall, IVIG products showed a high level of reactivity against the studied pathogens, regardless the geographical origin (i.e. measles, diphtheria, tetanus, Epstein-Barr and CMV). However, in countries from North America and Pacific, a cluster of relatively higher titers for different pathogens including Parainfluenza, Influenza B, Epstein-Barr, Varicella and Measles, were observed. IVIG products form Asiatic countries were in the lower titer range for the same pathogens. In India, high antibody levels against Dengue, Chikungunya, West Nile Virus, Hepatitis A and E were observed. The authors suggested that vaccination programs and incidence of pathogens might have an impact on IVIG antibody titers of a particular region.

This year's Nobel Laureate Yoshinori Ohsumi discovered mechanisms underlying autophagy, a process for degrading and recycling cellular components. Autophagy, is also known to contribute to cell intrinsic immunity against viral infection. An impairment of herpes simplex virus 1-induced selective autophagy was described by Liyana Ahmad from the Imperial College London, Department of Virology, London, United Kingdom, in patients with herpes simplex encephalitis. ■

Disclosure Statement: The author has no conflicts of interest to disclose.

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