Giovanni Ferrara1, Davide Valentini2, Martin Rao2, Jan Wahlström3, Johan Grunewald1, Lars-Olof Larsson4, Susanna Brighenti5, Ernest Dodoo6, Alimuddin Zumla7, Markus Maeurer8. 1. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Solna, Sweden. 2. Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden; Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge 14186, Stockholm, Sweden. 3. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 4. Angered's Hospital, Gothenburg, Sweden. 5. Centre for Infectious Medicine (CIM), Department of Medicine (MedH), Karolinska Institutet, Stockholm, Sweden. 6. Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge 14186, Stockholm, Sweden. 7. Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. 8. Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden; Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge 14186, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
Abstract
INTRODUCTION: Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. METHODS: Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. RESULTS: Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosis patient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosis patient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosis patient sera. CONCLUSIONS: Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy.
INTRODUCTION:Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. METHODS: Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. RESULTS: Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosispatient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosispatient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosispatient sera. CONCLUSIONS: Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosispatients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy.
Authors: Susanna L Lundström; Tina Heyder; Emil Wiklundh; Bo Zhang; Anders Eklund; Johan Grunewald; Roman A Zubarev Journal: Int J Mol Sci Date: 2019-05-01 Impact factor: 5.923