Artemio M. Jongco

Immunodeficiencies Associated with Abnormal Newborn Screening for T Cell and B Cell Lymphopenia

Newborn screening for SCID has revealed the association of low T cells with a number of unexpected syndromes associated with low T cells, some of which were not appreciated to have this feature. This review will discuss diagnostic approaches and the features of some of the syndromes likely to be encountered following newborn screening for immune deficiencies.

X-linked agammaglobulinemia presenting as polymicrobial pneumonia, including Pneumocystis jirovecii

Pneumocystis jirovecii pneumonia is an opportunistic pulmonary infection usually associated with T-cell defects. Clinical and murine studies demonstrate that B-cells and Pneumocystis-specific antibodies also contribute to effective immune responses.1 Patients with primary humoral immunodeficiencies, including X-linked agammaglobulinemia (XLA), may develop P . jirovecii pneumonia despite normal T-cell number and function.2,3 XLA arises from Bruton tyrosine kinase (BTK) gene mutations, leading to pre-B-cell differentiation arrest, absence of immunoglobulin expression, and increased susceptibility to bacterial/enteroviral infections.4 Although more than 600 BTK mutations have been described, new variations/mutations continue to be identified. We describe an infant with a novel BTK kinase domain variation who presented with polymicrobial pneumonia, including P. jirovecii.

The Importance of Measuring IL10 Levels in Patients with Suspected IL10/IL10R Defects

To the Editor: Interleukin 10 (IL-10) is an anti-inflammatory cytokine that is critical tomaintain immune homeostasis in the gastrointestinal tract. Its immunosuppressive effects include the restriction of T cell proliferation, limitation of pro-inflammatory cytokine production, and the downregulation of co-stimulatory protein expression on antigen presenting cells [1]. IL-10 signaling occurs through a heterotetrameric IL-10 receptor (IL10R) complex comprised of IL-10R1 and IL-10R2. IL-10 receptor deficiency is a rare primary immunodeficiency that typically presents early in life with inflammatory bowel disease, folliculitis, multiple abscesses, perianal fistulas, arthritis, and recurrent respiratory diseases [1]. This is caused by loss-of-function mutations in the genes encoding for the IL-10 receptor (IL10R) [2]. The histopathology of affected individuals demonstrates intestinal mucosa ulcers with epithelial inflammatory infiltrates and abscesses. Patients with IL10 deficiency often have minor immunologic abnormalities, including normal or slightly decreased serum immunoglobulin levels, decreased CD4+/CD8+ T cell ratios, and variations in T cell, B cell, and NK cell numbers. Individuals with IL-10 or IL-10R deficiency are typically unresponsive to immunosuppressive therapy. The only known treatment that is curative in these patients is hematopoietic stem cell transplantation (HSCT) [3]. To our knowledge, assessing serum IL-10 levels to attribute a potential signaling defect to the IL-10 receptor has not been previously described in children with IL-10R mutations. This paper describes a patient with IL-10R deficiency that was found to have a high serum IL-10 level as part of his initial immunological evaluation, raising suspicion for the eventual diagnosis of IL-10 receptor deficiency. A 4-year-old Turkish male, the product of a first-cousin consanguineous marriage, with a past medical history of partial central diabetes insipidus, cortical blindness, and global developmental delay, was initially seen in our Allergy clinic at the age of 1 year old with a diagnosis of milk protein proctocolitis secondary to the detection of blood in his stool. The patient subsequently failed an oral challenge to milk and was diagnosed with non-IgE-mediated milk allergy with a negative Immunocap at that time. He remained well on a milk-free diet for the next 2 years. At the age of 3 years, he was hospitalized with oral aphthous ulcers, persistent diarrhea with intermittent hematochezia, perirectal fissures and ulcerations. Gastrointestinal evaluation included an upper endoscopy that revealed aphthous ulcers in the esophagus and duodenum, and a colonoscopy revealed deep ulcers and friable mucosa throughout the colon. Mucosal histology demonstrated acute esophagitis, and focal areas of active ileitis and colitis. He was given a diagnosis of inflammatory bowel disease (IBD) and was placed on an elemental formula diet, antimicrobial therapy and topical steroids for the perirectal disease. He was evaluated in our Immunology clinic and a subsequent workup revealed normal quantitative immunoglobulins, T cell numbers and subpopulations and dihydrorhodamine (DHR) assay that ruled out chronic granulomatous disease. He also had a normal level of glucose 6-phosphate dehydrogenase, a positive * Susanne LaBarba svera1@northwell.edu