Abstract 52 Allergy, Immunology, and Rheumatology Poster Symposium, Sunday, 5/2
Severe disseminated infections with poorly pathogenic intracellular bacteria such as atypical mycobacterium and Salmonellaspecies have been reported in individuals with no identifiable immune defects by conventional immune workup. Recent studies revealed that genetic defects in these patients are commonly associated with IFNγ and IL-12 cytokine network. These include impaired IFNγ production due to IL-12p40 production defect or deficiency of IL-12 receptor (IL-12R) beta1 chain or unresponsiveness to IFNγ due to IFNγ receptor deficiency. Herein, we report the case of necrotizing granulomatous lymphadenitis by Mycobacteroium avium (MA) with impaired IL-12 dependent IFNγ production albeit intact IL-12R expression. This 2 year old Caucasian female was initially evaluated for potential immunodeficiency secondary to suspected but ill-defined immunodeficiency in her older siblings, one of them deceased 10 yrs ago (recurrent arthritis and possible autoimmune myocarditis). This child had right cervical lymph adenopathy since 15 months of age, but had no other history of serious illness requiring hospitalization. Conventional immune workup revealed normal immune functions with regard to T and B cell numbers, antibody production, Ig levels, thymidine incorporation with mitogen stimuli, NBT, and chemotaxis. She had negative HIV antibody. She was found to be strongly reactive to PPD (> 10 × 10 mm) in spite of no risk factors. Excised cervical lymph nodes (LN) revealed severe necrotizing granulomatous lesions growing MA. Her peripheral blood mononuclear cells produced little IFNγ in response to PHA and exogenous IL-12p70 (functional IL-12). IL-12p40 production was rather elevated with intact expression of IL-12R (β1 and 2 chains) by immunofluorescence. Similar results were also found in two of her siblings; poor response to exogenous IL-12 with respect to IFNγ production and thymidine incorporation but elevated IL-12p40 production. This patient had adverse reactions to multiple anti-mycobacterium medications to which the MA grown was sensitive. This made it very difficult to control her MA infection, resulting in persistent drainage at the site of surgical excision. The patient was then treated with exogenous IFNγ like those with chronic granulomatous disease. She responded very well to exogenous IFNγ with rapid healing of the excision site. This case may indicate an another defect in IL-12 and IFNγ network resulting in persistent atypical mycobacterial infection and potent PPD reactivity compatible with tuberculosis. Strongly positive PPD reactivity may not rule out atypical mycobacterium infection in these patients with defects in IFNγ and IL-12 network.
This study was partly funded through a grant from Lion's Multiple 5M Hearing Foundation.
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Jyonouchi, H., Kelly, A., Ferrieri, P. et al. A Case of Necrotizing Granulomatous Lymphadenitis with Mycobacterium avium; Impaired IL-12 Dependent IFN-γProduction with Apparent Intact Expression of IL-12 Receptor (β1 and β2 Chains). Pediatr Res 45, 10 (1999). https://doi.org/10.1203/00006450-199904020-00069