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OBJECTIVES: Common variable immunodeficiency (CVID) is associated with a spectrum of autoimmune complications. We studied the prevalence of gastrointestinal (GI) manifestations and infections in patients with CVID. METHODS: Complete clinical data of 132 Finnish patients with CVID (106 probable and 26 possible CVID) followed up between 2007 and 2016 were collected to a structured database. Data on endoscopies, histology, and laboratory studies were retrieved from patient files. RESULTS: Most common referral indications were diarrhea and/or weight loss (47%–67%). Patients with probable CVID had higher fecal calprotectin and α1-antitrypsin and lower blood vitamin B12 than patients with possible CVID. Gastroscopy and colonoscopy were done to 71 (67%) and 63 (59%) patients with probable CVID, respectively. Endoscopies showed that 15% of them had chronic active gastritis and 17% atrophic gastritis and 3% had gastric adenocarcinoma. A celiac sprue-like condition was found in 7 patients (10%), of whom 3 responded to a gluten-free diet. Colonoscopies demonstrated unspecific colitis (14%), ulcerative colitis (8%), microscopic colitis (10%), and Crohn's disease (2%). Colonic polyps were noted in 30% of patients, and 3% had lower GI malignancies. Thirty-five patients with CVID had bacterial or parasitic gastroenteritis; chronic norovirus was detected in 4 patients with probable CVID. Patients with GI inflammation had higher levels of fecal calprotectin and blood CD8 + T lymphocytes but lower counts of CD19 + CD27 + memory B cells and/or CD19 + B cells. Immunophenotype with low B-cell counts was associated with higher fecal calprotectin levels. DISCUSSION: Patients with CVID had a high prevalence of GI manifestations and infections of the GI tract. GI inflammation was associated with a distinct immunophenotype and elevated fecal calprotectin.

Treatment of infective endocarditis (IE) should be initiated promptly. This might hamper the chances to identify the causative organism in blood cultures. Microbiological sampling of infected valve in patients undergoing surgery might identify the causative organism. The impact of pre-operative antimicrobial treatment on the yield of valve samples is not known. This study evaluated the impact of the duration of the pre-operative antibiotic treatment on valve culture and 16S rRNA PCR findings from resected endocardial samples. Patients meeting the modified Duke criteria of definite or possible IE and undergoing valve surgery due to IE during 2011–2016 were included from Southern Finland. Eighty-seven patients were included. In patients with shorter than 2 weeks of pre-operative antimicrobial treatment, PCR was positive in 91% ( n = 42/46) and valve culture in 41% ( n = 19/46) of cases. However, in patients who had 2 weeks or longer therapy before operation, PCR was positive in 53% ( n = 18/34) and all valve cultures were negative. In 14% of patients, PCR had a diagnostic impact. In blood-culture negative cases ( n = 13), PCR could detect the causative organism in ten patients (77%). These included five cases of Bartonella quintana , one Tropheryma whipplei , and one Coxiella burnetii . Long pre-operative antimicrobial treatment was shown to have a negative impact on microbiological tests done on resected endocardial material. After 2 weeks of therapy, all valve cultures were negative, but PCR was positive in half of the cases. PCR aided in diagnostic work-up, especially in blood culture negative cases. Electronic supplementary material The online version of this article (10.1007/s10096-018-03451-5) contains supplementary material, which is available to authorized users.

BackgroundThe telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs.MethodsClinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions.ResultsIn four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients.ConclusionsOur results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0864-9) contains supplementary material, which is available to authorized users.

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 k 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 f 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 f 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 YO f 2 YO to 21 % f 13 YO) and class I1 (from 20 YO & 9 Yo to 43 % f 13 Yo) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection.

Background Health care-associated infective endocarditis (HAIE) and intravenous drug use-related IE (IDUIE) have emerged as major groups in infective endocarditis (IE). We studied their role and clinical picture in population-based survey. Methods A population-based retrospective study including all adult patients diagnosed with definite or possible IE in Southern Finland in 2013-2017. IE episodes were classified according to the mode of acquisition into three groups: community-acquired IE (CAIE), HAIE and IDUIE. Results Total of 313 episodes arising from 291 patients were included. Incidence of IE was 6.48/100,000 person-years. CAIE accounted for 38%, HAIE 31% and IDUIE 31% of IE episodes. Patients in IDUIE group were younger, they had more frequently right-sided IE (56.7% vs 5.0%, P<0.001) IE and S. aureus as etiology (74.2% vs 17.6%, P<0.001) compared to CAIE group. In-hospital (15.1% vs 9.3%, P=0.200) and cumulate one-year case-fatality rates (18.5% vs 17.5%, P=0.855) were similar in CAIE and IDUIE. Patients with HAIE had more comorbidities, prosthetic valve involvement (29.9% vs 10.9%, P=0.001), enterococcal etiology (20.6% vs 5.9%, P=0.002) and higher in-hospital (27.8% vs 15.1%, P=0.024) and cumulative one-year case-fatality rate (43.3% vs 18.5%, P<0.001) than patients with CAIE. Staphylococcus aureus caused one-fifth of IE episodes in both groups. Conclusion Our study indicates that in areas where injection drug use is common IDUIE should be regarded as a major risk group for IE along with HAIE and not seen as part of CAIE. Three different risk groups, CAIE, HAIE and IDUIE, with variable characteristics and outcome should be recognized in IE.

Common variable immunodeficiency and other late-onset immunodeficiencies often co-manifest with autoimmunity and lymphoproliferation. The pathogenesis of most cases is elusive, as only a minor subset harbors known monogenic germline causes. The involvement of both B and T cells is however implicated. To study whether somatic mutations in CD4+ and CD8+ T cells associate with immunodeficiency, we recruited 17 patients and 21 healthy controls. Eight patients had late-onset common variable immunodeficiency and nine patients other immunodeficiency and/or severe autoimmunity. In total, autoimmunity occurred in 94% and lymphoproliferation in 65%. We performed deep sequencing of 2533 immune-associated genes from CD4+ and CD8+ cells. Deep T-cell receptor beta sequencing was used to characterize CD4+ and CD8+ T-cell receptor repertoires. The prevalence of somatic mutations was 65% in all immunodeficiency patients, 75% in common variable immunodeficiency and 48% in controls. Clonal hematopoiesis-associated variants in both CD4+ and CD8+ cells occurred in 24% of immunodeficiency patients. Results demonstrated mutations in known tumor suppressors, oncogenes, and genes that are critical for immune- and proliferative functions, such as STAT5B (two patients), C5AR1 (two patients), KRAS (one patient), and NOD2 (one patient). Additionally, as a marker of T-cell receptor repertoire perturbation, common variable immunodeficiency patients harbored increased frequencies of clones with identical complementarity determining region 3 sequences despite unique nucleotide sequences when compared to controls. In conclusion, somatic mutations in genes implicated for autoimmunity and lymphoproliferation are common in CD4+ and CD8+ cells of patients with immunodeficiency. They may contribute to immune dysregulation in a subset of immunodeficiency patients.

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