By Esther de Vries
Dear ESID members,
I would like to draw your attention to two papers concerning antibody deficiency that are maybe not so spectacular but may have implications for the care issued to this large group of patients.
In the August 2014 issue of Frontiers in Immunology, Smith et al describe the use of the T-cell dependent Bacteriophage ΦX 174 as a diagnostic immunization in patients with antibody deficiency who are on immunoglobulin replacement (PubMed PMID: 25221555 – read the Abstract). This is not a novel idea, responses to Bacteriophage ΦX 174 were already studied in the ‘70s. However, the authors from the Duke Immunology Clinic show with their retrospective analysis of all 126 patients who were studied in this way between 1976 and 2012 that nineteen patients could be taken off their immunoglobulin replacement therapy based on a normal response to Bacteriophage ΦX 174 immunization (0.022 mL/kg intravenously, given 1-4 times, to study primary as well as memory responses). Hypogammaglobulinemia patients form a large and heterogeneous group, diagnostic criteria are not well defined. It is often difficult to decide whether immunoglobulin substitution is justified in these cases. In pediatric patients, this is further complicated by the fact that it may ‘simply’ be a case of transient hypogammaglobulinemia of infancy (THI), but it may also be a case of developing common variable immunodeficiency (CVID). The product is not licensed for routine medical use, however, they showed that adverse events were minor, and present in only 14 of 171 administrations where they had enough information to study this.
Not many clinical papers are published concerning this patient group; I found one in the August 2013 issue of the Mayo Clinic Proceedings. Sang-Hwa Urm et al retrospectively ascertained the asthma status in patients with 26 sIgAD and 13 CVID cases identified in Olmsted County, MN, from 1964 to 2008 (PubMED PMID: 23910409 – read the Abstract). They compared each case to four age- and sex-matched controls from the community (2) and from individuals (2) who had undergone an immunological work-up which was normal. 23% of cases as compared to 10% of controls had a history of asthma prior to the immunological diagnosis. This is an interesting viewpoint, coinciding with my personal experience in the clinic. However, unfortunately, the authors do not at all discuss the important point whether ‘asthma’ in these charts was truely asthma, or antibody deficiency related airway disease mislabeled as such.
All in all, my search on this topic strengthened my feeling that a lot more clinical research is needed in this patient group, especially in those many patients that do not have a monogenetic diagnosis like XLA or a form of hyper-IgM syndrome. The new ESID registry is hopefully going to be a good tool for this!
Esther de Vries