Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren's syndrome using high-content peptide microarrays.
BACKGROUND
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.
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Solna, Sweden.
Giovanni
G
Ferrara
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.
Davide
D
Valentini
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.
Martin
M
Rao
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Jan
J
Wahlström
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Solna, Sweden.
Johan
J
Grunewald
Angered's Hospital, Gothenburg, Sweden.
Lars-Olof
LO
Larsson
Centre for Infectious Medicine (CIM), Department of Medicine (MedH), Karolinska Institutet, Stockholm, Sweden.
Susanna
S
Brighenti
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge 14186, Stockholm, Sweden.
Ernest
E
Dodoo
Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
Alimuddin
A
Zumla
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.
Markus
M
Maeurer
D000917:Antibody Formation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods*; D012507:Sarcoidosis / Q000097:blood / Q000276:immunology*; D013577:Syndrome
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010455:Peptides
Humoral immune responses; Löfgren’s syndrome; Peptide microarray; Sarcoidosis; Tuberculosis; tuberculosis antigens