The patient, a male from Mexico born to unrelated parents, presented at 20 days old with erythematous macules, scaly plaques, generalized alopecia, purulent otorrhea, cervical lymphadenopathy, hepatomegaly, and eosinophilia. At 4 months, he developed meningitis without an identified pathogen, anemia, and lymphocytosis, treated with broad-spectrum antibiotics. Immunoglobulin levels were IgG 790, IgM 110, IgA 324, and IgE 14.3 mg/dL. A thymus ultrasound showed hypoplasia (1.6 × 0.8 mm).
At 1 year, he experienced gastrointestinal infection and autoimmune thrombocytopenic purpura (platelets 15 x 103), which resolved with immunosuppressants. He missed medical follow-ups for 7 years. At 8, he suffered community-acquired pneumonia requiring antibiotics and oxygen therapy, with a recurrence six months later. At 9, dental caries and molluscum contagiosum were noted. At 10, he was hospitalized for severe varicella and pneumonia, treated with acyclovir, ceftriaxone, and vancomycin.
Lymphocyte counts revealed CD3+ 808, CD4+ 428, CD8+ 380, CD19+ 333, and CD16+56+ 974 cells/μL. Lung CT showed fungal infection; Aspergillus montevidensis was identified in bronchoalveolar fluid culture, with antigen measurement of 0.94 IDO. He improved with voriconazole, caspofungin, and posaconazole. Nail onychodystrophy was noted during hospitalization.
Severe infections prompted evaluation for immune disorders. Genetic testing identified a heterozygous pathogenic FOXN1 variant (c.1448_1451del, p.Ala483Glyfs*66). Given the link between thymic defects and type I interferon autoantibodies, these were measured due to suspected immune dysfunction.
Interferon-alpha and omega autoantibodies were detected in the patient’s plasma using Bio-Plex (Luminex). Neutralizing capacity was confirmed in vitro via STAT-1 phosphorylation assays. The patient’s STAT-1 response to IFN-alpha 2 and IFN-omega was significantly reduced, indicating neutralization, even at high IFN concentrations, while IFN-beta remained unaffected.
Phosphorylation of STAT-1 (p-STAT1) tyrosine 701 (Y701).
