Time to Think About Anti-Cytokine Autoantibodies

Introduction Recently, neutralizing autoantibodies against different cytokines have been found to explain susceptibility to infections. Because the clinical pictures mimic innate immune disorders (IIDs), they have been defined as phenocopies of IIDs. Autoantibodies against GM-CSF have recently been associated with disseminated cryptococcosis and alveolar proteinosis. Clinical Case The patient was a 17-year-old female with no family or personal history of disease. She presented with clinical symptoms for one year, characterized by fainting episodes, headaches, and vomiting. She underwent multiple medical evaluations, but no diagnostic conclusions were reached. Over time, the headache intensity increased and was associated with fever, asthenia, refusal of food, and subcutaneous lesions on the abdomen and chest that appeared to be lipomas. Ultimately, her condition was associated with mastitis, a solid nodule, and inflamed lymph nodes in the axillary regions. The biopsy revealed chronic granulomatous mastitis with Langhans giant cells and structures consistent with Cryptococcus spp. The cytochemical study of the cerebrospinal fluid showed hyperproteinorrhea and hypoglycorrhachia. The brain MRI revealed a lesion in the right basal ganglia related to cryptococcosis. Disseminated cryptococcosis was confirmed, and she completed six weeks of amphotericin B. It was suspended due to kidney damage and changed to fluconazole, which remains on to date. The immunological approach included a complete blood count, immunoglobulins, and lymphocyte subpopulations with normal values for her age. The autoimmunity approach and HIV test were negative. Antibodies against cytokines were requested, with identification of anti–GM-CSF autoantibodies. Discussion In all patients with disseminated cryptococcosis, we must look for immunological abnormalities. If no monogenic defects are found, we must look for autoantibodies against GM-CSF. In Mexico, we have implemented this search in the immunodeficiency laboratory. Patients may develop alveolar proteinosis, so they should be followed up by a pneumologist. Autoantibodies are compatible with autoimmunity, so treatment is immunosuppressive and immunomodulatory.