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Berlin, Germany

Ulrich R.G.,Institute For Neue Und Neuartige Tierseuchenerreger | Ulrich R.G.,University of Federal Defense Munich | Essbauer S.S.,Charite - Medical University of Berlin | Kruger D.H.,Labor Berlin GmbH | And 2 more authors.
Chirurgische Praxis

Rodents (and other small mammals) play a major role in the transmission of various zoonotic pathogens. This includes pathogens, directly or indirectly transmitted to humans by urine, indirectly transmitted by aerogen uptake of pathogen-contaminated dust or by arthropod vectors. On the other hand, transmission can be mediated by biting or by contact with the coat of the infected reservoir animal. For additional pathogens it is currently unknown, if they are pathogenic to humans or if rodents have an epidemiological role for their transmission to humans. This manuscript provides an overview for rodentborne zoonotic pathogens present in Germany: Hantaviruses, orthopox viruses, tick-borne encephalitis virus, Leptospira and Rickettsia spp. Source

Matz M.,Charite - Medical University of Berlin | Fabritius K.,Charite - Medical University of Berlin | Lorkowski C.,Charite - Medical University of Berlin | Durr M.,Charite - Medical University of Berlin | And 17 more authors.

Background. MicroRNAs (miRNAs, miR) hold important roles in the posttranscriptional regulation of gene expression. Their function has been correlated with kidney disease, and they might represent a new class of biomarkers for frequent evaluation of renal graft status.We analyzed their potential in identifying severe Tcell-mediated vascular rejection (TCMVR) (Banff 4-II/III) in kidney transplanted patients. Methods. Microarray experiments and semiquantitative real-time reverse transcription polymerase chain reaction were performed with total RNA isolated from blood cells of kidney graft recipients. Initialmicroarray analysis revealed 23 differentially expressed miRNAs distinguishing patients with TCMVR from patients with stable grafts. From these, we validated and further determined the expression of 6 differentially expressed miRNAs and 2 control miRNAs in 161 samples from patients with T cell-mediated rejection (Banff 3-Borderline, Banff 4-I/II/III), Banff-2 antibody-mediated rejection, Banff-5 interstitial fibrosis/tubular atrophy, in samples from stable patients and in samples from patients with urinary tract infection using real-time reverse transcription polymerase chain reaction. Results. Expression levels of all 6 candidate miRNAs were significantly downregulated in blood of TCMVR patients compared to the other groups and displayed high sensitivities and specificities for diagnosing TCMVR. The combination of 5miRNAs, identified by an unbiased multivariate logistic regression followed by cross-validation, enhanced the sensitivity and specificity for the diagnosis of TCMVR after renal transplantation. Conclusions. The combined measurement of miRNA-15B, miRNA-16, miRNA-103A, miRNA-106A, and miRNA-107 may help to better identify TCMVR after renal transplantation in a precise and clinically applicable way. © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Derganova O.,Charite - Medical University of Berlin | Derganova O.,Voronezh State Medical Academy | Martinez-Gamboa L.,Charite - Medical University of Berlin | Egerer K.,Charite - Medical University of Berlin | And 9 more authors.
Clinical and Experimental Rheumatology

Objective: Antibodies against citrullinated antigens (ACPA) represent one rheumatoid arthritis (RA) classification criteria. Recently, mutated and citrullinated vimentin (MCV), containing approx. 45 potentially citrullinated sites, was characterised as another modified autoantigenic RA target. Therefore, we wanted to screen, select and validate predominant MCV autoantigenic epitopes (called here MCE) as possible new diagnostic targets. Methods: MCV-derived peptides with citrullinated sites were screened in healthy controls and patients. Based on this, twelve selected MCE were used for validation of ACPA isotypes (IgA/IgG/IgM) with ELISA in early RA (ERA, <12 months) and established RA (>12 months) Russian patients. Sensitivity of MCE reactivity was compared to commercially available ELISAs for anti-CCP IgG, anti-MCV IgG, and anti-RF IgA/IgM/IgG. Results: Anti-MCE IgG/IgA//IgM antibodies were observed in 64.1%, 23.1%, and 15.4% ERA, and 63.9%, 26.7%, and 13.1% established RA patients, respectively. Anti-MCV IgG was present in 64.1% ERA and 55.0% RA patients. Furthermore, anti-CCP IgG and RF IgG/IgA/IgM were detectable in up to 76.9%, 71.8%, 71.8%, and 38.5% ERA, and 80.1%, 72.3%, 67.5%, and 43.0% RA patients. Anti-CCP IgG single positivity was observed in 7.7% ERA and 6.3% RA patients. Only one RA patient was anti-MCE single positive. Conclusion: MCV autoantigenic epitopes were emulated by cyclic citrullinated MCV-derived peptides and recognised by all autoantibody-Ig subclasses in RA. Tested MCE were recognized more frequently by IgG as the original MCV antigen. High antibody prevalence against CCP epitopes suggests a strong CCP-linkage to RA pathogenesis in the investigated Russian cohort. © Clinical and Experimental Rheumatology 2014. Source

von der Hagen M.,TU Dresden | Hennermann J.B.,Johannes Gutenberg University Mainz | von Bernuth H.,Charite - Medical University of Berlin | von Bernuth H.,Labor Berlin GmbH | And 3 more authors.
Medizinische Genetik

Microcephaly affects 2–3 % of the population and is often associated with intellectual disability. The underlying reduction in brain volume can result from various exogenous factors or genetic causes. Microcephaly remains a poorly defined condition lacking both uniform diagnostic approaches and classification. A definite etiological diagnosis is the key to predict the prognosis, identify co-morbidities and offer genetic counseling. In addition, the identification of the underlying cause increases our knowledge of brain development and the clinical spectrum of microcephaly. We propose a diagnostic approach for children with microcephaly from a pediatric neurologist point of view. © 2016, Springer-Verlag Berlin Heidelberg. Source

Lindenberg L.,Charite - Medical University of Berlin | Spengler L.,Charite - Medical University of Berlin | Bang H.,Orgentec Diagnostika | Dorner T.,Charite - Medical University of Berlin | And 10 more authors.
Arthritis Research and Therapy

Introduction: Antibodies against mutated citrullinated vimentin (AMCV) represent a useful diagnostic marker with correlation to disease activity in patients with rheumatoid arthritis (RA). Since seropositivity for citrullinated autoantibodies was predictive for response to B-cell depleting therapy (BCDT) with rituximab (RTX), we investigated whether differences in antibody fine reactivity and immunoglobulin (Ig) isotype kinetics among AMCV-positive patients could provide additional information about outcome. Methods: A total of 50 AMCV IgG-positive RA patients (RTX responders (RRs) n = 37 and non-responders (NRRs) n = 13) were analyzed for reactivity against MCV epitopes and co-existent AMCV isotypes IgM and IgA. Antibody titers were determined by enzyme-linked immunosorbent assay at baseline and 24 weeks after the first cycle of RTX, and compared to kinetics of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptide (ACCP). Results: Recognized MCV epitopes by AMCV IgG of RRs and NRRs showed similar baseline patterns, with reducing reactivity in RRs and unchanged or even expanding reactivity in NRRs upon RTX treatment. At baseline, RRs were more frequently negative for AMCV subtypes, especially for IgA (68 %), compared to NRRs (31 %). Being AMCV IgA-negative at baseline indicated a good treatment response to RTX (negative predictive value = 0.86). Co-existence of AMCV IgA and IgG with stable titers upon treatment were associated with poorer responses to RTX. Furthermore, reductions of AMCV IgA levels upon RTX correlated with the improvement of 28-joint Disease Activity Score (DAS28). In comparison, subtypes of RF and ACCP were not of additional value for prediction of RTX response. Conclusions: Restrictive IgG seropositivity against MCV with treatment-associated decline in fine reactivity and titers was predictive for response to RTX. Double-positivity for AMCV IgG and IgA was associated with failure to respond to BCDT, suggesting a pathogenetic and less sensitive IgA-producing B-cell subset in NRRs. © 2015 Lindenberg et al. Source

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