A 19-year-old US-born college student with a past medical history significant for ulcerative colitis treated with infliximab for the past 3 years and negative tuberculin skin test at initiation of TNFA was evaluated for a 3-month history of fever, night sweats, weight loss, productive cough, and abdominal pain. Several weeks prior to evaluation, she was treated for community-acquired pneumonia with azithromycin without symptomatic improvement. She was additionally treated with a short course of ciprofloxacin and prednisone for possible ulcerative colitis exacerbation without improvement. She had no known TB exposure including prior travel to endemic TB areas.
Physical examination revealed an afebrile woman in mild distress. Vital signs were notable for mild hypoxia (Spo2 = 92% on room air). She had no palpable lymphadenopathy. Bilateral rhonchi were present on pulmonary auscultation. Remainder of physical examination was unremarkable.
Laboratory evaluation revealed a normal complete blood count and inflammatory markers. Human immunodeficiency virus (HIV) testing was negative. QuantiFERON-TB Gold in-Tube (QFT) test was positive (2.62 IU/mL). Transbronchial lung biopsy and bronchoalveolar lavage showed acid-fast bacilli, and subsequent cultures grew pan-sensitive MTB. Computed tomography of the chest, abdomen, and pelvis revealed miliary pulmonary pattern, patchy nodular infiltrates, and mediastinal lymphadenopathy with peritoneal and omental involvement (Figure 1). She did well after completion of 6 months of anti-TB therapy.
In addition to the clinical QFT test, peripheral blood mononuclear cells (PBMCs) were analyzed by FC as part of a research study. This research study was approved by Mayo Clinic Institutional Review Board (Mayo IRB number 09-003253 00). Peripheral blood mononuclear cells were isolated by Ficoll-Paque separation from 40 mL of heparinized blood within 1 hour of collection and cryopreserved in liquid nitrogen until stimulation. Multiparameter antigen stimulation with costimulatory antibodies (MTB-purified protein derivatives (PPD), region of difference 1 (RD1) peptide antigen [ESAT-6/CFP-10 peptide mix or specific MTB antigens], positive and negative controls) was completed. The PBMC sample and antigens were incubated for 48 hours at 37 C and then stained with fluorescent dye-conjugated anti-CD3, anti-CD4, anti-CD8, anti-CD25, and anti-CD134 antibodies and isotype controls. About 2 x 105 cells were analyzed by fluorescence-activated cell sorting (FACS) (BD FACSCanto) and gated using FlowJo software and Kaluza FC software. Detailed methods have been reported previously.
CD25+CD134+ co-expression was detected on 0.34% and 0.84% of RD1 peptide and PPD-stimulated CD3+CD4+ T cells, respectively (Figure 2). In addition, upregulation of CD25+CD134+ was present on 0.26% and 0.59% of RD1 peptide and PPD-stimulated CD3+CD8+ T cells, respectively. These results were in the range of untreated LTBI associated with an increased risk of TB reactivation, as previously described, and suggest possible active TB infection in an immunosuppressed and symptomatic patient.