Panida Sriaroon

Immunoglobulin Replacement Therapy for Primary Immunodeficiency

Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

IgM Repertoire Biodiversity is Reduced in HIV-1 Infection and Systemic Lupus Erythematosus.

Background: HIV-1 infection or systemic lupus erythematosus (SLE) disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 (CDRH3) sequence level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations (SHM) in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly neutralizing HIV-1 antibodies. Conclusion: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.

Biological Modulators in Eosinophilic Diseases

Eosinophils can regulate local and systemic inflammation, and their presence in higher numbers appears to play an important role in the pathology of various atopic and inflammatory diseases. Eosinophil maturation, recruitment, and survival depend on several cytokine regulators, including interleukin (IL)-5, IL-4, and IL-13 as well as growth factors such as GM-CSF. Over the last decade, the approach to treating eosinophilic diseases has changed greatly. A number of biologic modulators have been developed to target eosinophilic inflammatory pathways, and their usage has resulted in variable clinical improvement in the treatment of eosinophilic-associated conditions. Novel targeted therapies that are safe and effective for treating these disorders are being investigated. This review summarizes the clinical use of biologic agents that have been studied in clinical trials or approved for treating eosinophilic diseases.

Thoracic Duct Injury Resulting in Abnormal Newborn Screen

Measurement of T-cell receptor excision circles (TREC) in neonates has allowed for population-based screening of severe combined immunodeficiency and other disorders associated with T-cell lymphopenia. In addition to primary T-cell lymphopenic disorders, secondary causes of T-cell lymphopenia can be diagnosed with TREC analysis. We discuss the diagnostic evaluation of a patient with normal TREC analysis at birth that became abnormal after cardiac surgery. TREC analysis was performed by the Florida State Laboratory. Diagnostic evaluation and treatment were performed at All Childrens Hospital, St Petersburg, Florida. We identified a 38-day-old female patient with thoracic duct injury, which caused chylothorax and chylous ascites diagnosed after an abnormal newborn screen. Chylothorax was secondary to thoracic duct injury after cardiac surgery and led to severe lymphopenia and hypogammaglobulinemia. Thoracic duct ligation led to improved lymphocyte counts and normalization of immunoglobulin levels. Secondary causes of lymphopenia are detected with TREC assay that lead to abnormal newborn screen results. Many secondary causes of lymphopenia can be acquired with normal initial newborn screens that become abnormal over time.

Psychrobacter immobilis septicemia in a boy with X-linked chronic granulomatous disease and fulminant hepatic failure.

A 16-year old boy with chronic granulomatous disease (CGD) developed Psychrobacter immobilis septicemia during a course of fulminant hepatic failure. The patient died despite aggressive management with antimicrobials and corticosteroids. While Psychrobacter immobilis rarely affects humans, it should be considered an organism that can cause sepsis in patients with CGD.

Intensive educational course in allergy and immunology.

A one‐day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows‐in‐training.