TY  - JOUR
A1  - Bumiller-Bini Hoch, Valéria
A1  - Kohler, Ana Flávia
A1  - Augusto, Danillo G.
A1  - Lobo-Alves, Sara Cristina
A1  - Malheiros, Danielle
A1  - Cipolla, Gabriel Adelman
A1  - Winter Boldt, Angelica Beate
A1  - Braun-Prado, Karin
A1  - Wittig, Michael
A1  - Franke, Andre
A1  - Pföhler, Claudia
A1  - Worm, Margitta
A1  - van Beek, Nina
A1  - Goebeler, Matthias
A1  - Sárdy, Miklós
A1  - Ibrahim, Saleh
A1  - Busch, Hauke
A1  - Schmidt, Enno
A1  - Hundt, Jennifer Elisabeth
A1  - Araujo-Souza, Patrícia Savio de
A1  - Petzl-Erler, Maria Luiza
T1  - Genetic associations and differential mRNA expression levels of host genes suggest a viral trigger for endemic pemphigus foliaceus
JF  - Viruses
N2  - The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.
KW  - endemic pemphigus foliaceus
KW  - virus
KW  - genetic association
KW  - differential gene expression
KW  - autoimmune disease
KW  - environmental factors
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270572
SN  - 1999-4915
VL  - 14
IS  - 5
ER  - 
TY  - JOUR
A1  - Porubsky, Stefan
A1  - Popovic, Zoran V.
A1  - Badve, Sunil
A1  - Banz, Yara
A1  - Berezowska, Sabina
A1  - Borchert, Dietmar
A1  - Brüggemann, Monika
A1  - Gaiser, Timo
A1  - Graeter, Thomas
A1  - Hollaus, Peter
A1  - Huettl, Katrin S.
A1  - Kotrova, Michaela
A1  - Kreft, Andreas
A1  - Kugler, Christian
A1  - Lötscher, Fabian
A1  - Möller, Burkhard
A1  - Ott, German
A1  - Preissler, Gerhard
A1  - Roessner, Eric
A1  - Rosenwald, Andreas
A1  - Ströbel, Philipp
A1  - Marx, Alexander
T1  - Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: strong association with lymphomas and non-myasthenic autoimmune diseases
JF  - Cancers
N2  - Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32–80; lesion diameter 7.0 cm, 1–14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave’s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases.
KW  - autoimmune disease
KW  - imaging
KW  - LESA
KW  - lymphoma
KW  - myasthenia
KW  - pathology
KW  - surgery
KW  - thymus
KW  - thymic epithelial tumor
KW  - thymitis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223049
SN  - 2072-6694
VL  - 13
IS  - 2
ER  - 
TY  - JOUR
A1  - Strunz, Patrick-Pascal
A1  - Froehlich, Matthias
A1  - Gernert, Michael
A1  - Schwaneck, Eva Christina
A1  - Fleischer, Anna
A1  - Pecher, Ann-Christin
A1  - Tony, Hans-Peter
A1  - Henes, Joerg Christoph
A1  - Schmalzing, Marc
T1  - Immunological Adverse Events After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients
JF  - Frontiers in Immunology
N2  - Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p = .0433, Cohen’s d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p = .0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p = .0064, r = .65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES.
KW  - scleroderma
KW  - fever
KW  - autoimmune disease
KW  - Grave’s disease
KW  - modified Rodnan skin score (mRSS)
KW  - risk factor analysis
KW  - engraftment syndrome
KW  - Sjögren’s syndrome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245574
SN  - 1664-3224
VL  - 12
ER  -