31 Year Old Caucasian Male Presenting with Hypogammoglobulinemia and T/B-Cell Lymphopenia

Rationale: Lymphocytopenia in adults has a variety of etiologies and a broad differential diagnosis.  Here we present a 31 year old male with T/B-cell lymphocytopenia, hypogammoglobulinemia, and a unique immunologic phenotype that has been previously unreported in sarcoidosis.

Methods: Flow cytometry, TCR gamma by PCR, and gene sequencing

Results: Our patient presented after hospital evaluation for pneumonia revealed elevated ACE level, calcium, and hypogammoglobulinemia.  CT of chest showed multiple calcified lymph nodes, bronchiectasis, pneumatocele, scoliosis, and fibrosing mediastinitis.  Axillary lymph node biopsy showed multiple non-caseating granulomas.  Chart review revealed  absolute lymphocyte count of 400-600 for the past 7 years.  Lymphocyte subpopulation showed markedly decreased  absolute counts of CD4+, CD8+, CD19+, and CD20+ cells with normal NK cells.  Aberrant T-cell development was indicated by absence of naïve CD4+ T-cells, markedly decreased TREC, skewing of T-cell receptor (TCR) repertoire from alpha/beta to gamma/delta subset, and a clonal population of TCR gamma cells.  Antibody responses to streptococcus, tetanus and diphtheria were normal.  Lymphocytes proliferated to mitogens was normal. Bone marrow biopsy revealed non-caseating granulomas with lymphocytopenia (1%) but normal distribution.

Genetic sequencing of RAG1, RAG2, STAT3, and DOCK8 did not reveal any pathogenic mutations.  Patient was started on prednisone 60mg daily with decrease in pulmonary symptoms and normalization of calcium.

Conclusions: Here we present a case of a 31 year old caucasion male with sarcoidosis who presented with hypogammoglobulinemia, severe prolonged lymphocytopenia, hypercalcemia, and pneumonia/bronchiectasis.  Further evaluation revealed granulomas in multiple locations and a unique T-cell immunophenotype that has not been completely described before in sarcoidosis.