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Most patients with primary immune deficiency suffer from recurrent infections, however, paradoxical autoimmune phenomena can also manifest. The aim of this study was to identify immunological markers of autoimmune phenomena associated with common variable immunodeficiency (CVID). The study included 33 adults with CVID divided into two groups: (1) those with noninfectious autoimmune complications (CVID-C (n = 24)) and (2) those with only infectious symptoms (CVID-OI (n = 9)). Flow cytometry of peripheral blood was performed and compared with systemic lupus erythematosus (SLE) patients (n = 17) and healthy controls (n = 20). We found that all lymphocytes were lower in CVID-C and SLE. NK cells were lowest in CVID-C. Th17 cells were significantly reduced in CVID-C and SLE. Tregs were significantly lower in CVID-C and SLE. Bregs did not significantly differ between any groups. Class-switched memory B cells were significantly lower in CVID-C and CVID-OI. Lastly, plasmablasts were significantly higher in SLE. Among the T cell subsets, CVID-C patients had lower naive and recent thymic emigrant CD4+ T cells. In conclusion, reduced Treg, Th17, and NK cells are features of CVID with autoimmune complications, and class-switched memory B cells can help distinguish patients with different causes of autoimmunity. Future studies are needed to confirm whether reductions of Treg, Th17, and NK cells might be a biomarker of more complicated CVID cases.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) belongs to systemic autoinflammatory diseases (AIDs). Many of these syndromes are genetically conditioned and can be inherited. Diagnosis relies on clinical symptoms and should be confirmed by genetic testing. One of the most serious complications is AA amyloidosis. We present the diagnostic route of a 33-year-old male with AA amyloidosis and his children, leading to diagnosis of monogenic autoinflammatory syndrome, confirmed by genetic analysis. A novel variant of the in-frame insertion type in one allele of TNFRSF1A gene was found by whole exome sequencing and confirmed by Sanger sequencing, which allowed a diagnosis of TRAPS. Three-dimensional modeling was used to assess the structural changes introduced into TNFR1 molecule by the insertion. The analysis of the 3D model revealed that accommodation of the 4AA insert induces misalignment of three cysteine bridges (especially the C70-C96 bridge) in the extracellular domain, leading to putatively misfolded and improperly functioning TNFR1. Three of the patient&rsquo, s daughters inherited the same variant of the TNFRSF1A gene and presented TRAPS symptoms. TRAPS is a very rare disease, but in the presence of suggestive symptoms the genetic diagnostic workout should be undertaken. Early diagnosis followed by appropriate clinical management can prevent irreversible complications.

Silver-based materials are widely used in clinical medicine. Furthermore, the usage of silver containing materials and devices is widely recommended and clinically approved. The impact on human health of the increasing use of silver nanoparticles in medical devices remains understudied, even though Ag-containing dressings are known to release silver into the bloodstream. In this study, we detected a widespread and sometimes significant silver accumulation both in healthy and sick liver biopsies, levels being statistically higher in patients with various hepatic pathologies. 28 healthy and 44 cirrhotic liver samples were investigated. The median amount of 0.049 ppm Ag in livers was measured in cirrhotic livers while the median was 0.0016 ppm for healthy livers (a more than 30-fold difference). The mean tissue concentrations of essential metals, Fe and Zn in cirrhotic livers did not differ substantially from healthy livers, while Cu was positively correlated with Ag. The serum levels of gamma-glutamyl transpeptidase (GGTP) was also positively correlated with Ag in cirrhotic livers. The increased Ag accumulation in cirrhotic livers could be a side effect of wide application of silver in clinical settings. As recent studies indicated a significant toxicity of silver nanoparticles for human cells, the above observation could be of high importance for the public health.

Background Autoinflammatory diseases (AIDs) cover a spectrum of diseases, which lead to chronic or recurrent inflammation caused by activation of the innate immune system, typically in the absence of high titre autoantibodies.1 The most common monogenic AIDs are cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS). In hereditary AIDs, chronic and recurrent inflammation can lead to both acute disease and irreversible damage.2 Objectives To describe irreversible damage and diagnostic delay of AID in Polish adult patients (age≥18). Methods We rewieved the records of 11 Caucasian (2 women, 9 men) and one female patient with Middle Eastern ancestry followed in our center from Aug 2012 to Jan 2019. We analysed demographic features, diagnostic delay, previous diagnosis and organ damage3. Results Eleven patients had documented variant mutation and AID diagnosis (6-TRAPS, 4-CAPS, 1-FMF). One patient with AA amyloidosis had negative genetic results. The mean age of the patients at the time of disease onset was 9,1 years (0,1- 37) and 33 years (16-62) at diagnosis, In all Caucasian patients diagnosis was established after the age of 18. Previous diagnosis was: JIA (2), AOSD (2), UCTD (4), vasculitis (1), seronegative RA (1), FMF (3 finaly confirmed TRAPS) and allergy (3). Prior treatment included GCS (12/12), cDMARDS (7), antimalarials (6), colchcine (4), bDMARDS: tocilizumab-1, etanercept-2, adalimumab-1, CYC (2).After diagnosis 11 patients received IL-1 inhibitor, ankinra, Only one, 62 year old woman with TRAPS, did not need biological treatment. Only 3 TRAPS patients were free from damage accrual. We documented following damage categories: renal/amyloidosis (5 male cases), developmental (3 growth retardation), ear (severe hearing loss -3 CAPS cases). CINCA male patient at age 29 had multiple organ damage: neurological (epilepsy), severe hearing loss, severe ocular involvement (including optic nerve athrophy), joint restriction and deformity leading to complete physical disability. One FMF woman was adviced elective abortion, one MWS had miscarriage. Two of 3 women had history of malignancy (one: breast cancer and ovarian cancer, and another thyroid cancer). No any mental retardation occured. During follow up 2 male patients with extensive amyloidosis died despite anakinra treatment. Conclusion AID are misdiagnosed and have high risk of damage. We advocate the need for efforts in order to increase awarness of AID to reduce the diagnostic delay. The frequency of malignancy in AID should be addressed in future international collaborative studies. References [1] Masters SL, et al. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27:621–68. [2] Federici S, et al. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheumatic Dis 2015;74:799–805. [3] ter Haar NM, et al. Development of the autoinfammatory disease damage index. Ann Rheum Dis 2017;76:821–830 Disclosure of Interests None declared

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid diseases that occur after solid organ and bone marrow transplantation. Lung-located PTLD has been reported in recipients of the heart, cord blood stem cells, lungs, and bone marrow transplants, but only four cases were reported previously after kidney transplantation. Thoracic location of PTLD must be regarded as an especially dangerous complication. The pathogenesis, and clinical and histological features of PTLD remain poorly defined but predisposing risk factors are becoming better understood. Namely, Epstein-Barr virus (EBV) and immunosuppressive agents appear to be such risk factors. There has been marginal success in treating PTLD using a number of treatment modalities, including combination chemotherapy with anti-CD20 or high-dose chemotherapy with stem cell rescue. We report a renal allograft recipient transplanted in March 2000, diagnosed with EBV-associated and lung-located PTLD. His initial immunosuppression consisted of tacrolimus, azathioprine, and steroids. Azathioprine was withdrawn in September 2001. In November 2001 a high-resolution computed tomography scan revealed two round masses in the right lung. The patient underwent right thoracotomy and resection of the lower and middle lobe. The diagnosis of PTLD was settled by intraoperative histopathological evaluation. The postoperative histological assessment confirmed the diagnosis and revealed positive staining for EBV. The patient remained in complete remission for 3 years with a well-functioning renal allograft, with current serum creatinine of 1.2 mg%. This case illustrates that the treatment of lung-located PTLD may be successful, but it depends on a combination of prompt diagnosis, reduction of immunosuppression, and of course surgery.

Statins are effective to reduce total cholesterol and low-density lipoprotein fractions in a dose-dependent manner. Moreover, they have an excellent safety profile. Besides cholesterol-lowering properties, statins have additional actions described in the present case report. The diverse effects of these drugs means that many patients with different disease entities, such as cardiovascular diseases, can benefit from their effects. However, the problem of so called "class effect" remains controversial. The question whether each drug within the group is equivalent appears important, as long as statins must be taken long-term and as the therapy affects patient quality of life and survival. To address this question, we present two renal transplant recipients treated with statins. The induction of pharmacokinetic tolerance and damage to hepatic cells during administration of statins is discussed. Presented data suggest that the choice of statin should be based on individual patient requirements and adapted to the individual treatment response.

Rationale Relapsing polychondritis (RP) is a multisystemic, progressive disease of unknown etiology characterized by recurrent inflammation and progressive cartilage destruction. It can involve all types of cartilage including ears and nose, tracheobronchial tree, joints, and any other tissue rich in proteoglycans such as heart, eyes, and blood vessels. Recurrent chondritis can be life-threatening if the respiratory tract, heart valves, or blood vessels are affected. To date there is no data in the literature on the post solid organ transplantation RP. Patient concerns We present a 59-year-old male liver transplant recipient with primary sclerosing cholangitis who developed RP of the earlobes and nose despite post-transplant immunosuppression. Diagnoses Based on the clinical criteria, scintigraphy and biopsy from the left auricle his condition was diagnosed as RP. Interventions Pulses of methylprednisolone followed by high-dose oral steroids along with azathioprine were administered. Outcomes Such therapy diminished local cartilage inflammation, improved patient's general condition and the laboratory results. Significant loss of ear cartilage and characteristic "saddlenose" were observed after remission of acute symptoms. The control scintigraphy proved very good treatment response. Lessons To the best of our knowledge this is the first report on the RP in liver transplant recipient. Based on our patient presentation, we suggest that RP should be suspected in any transplant recipient with cartilage inflammation, and that the Michet's clinical criteria and scintigraphy seem to be the best diagnostic tools for solid organ transplant recipients suspected of RP.

Background Despite advances in immunosuppressive therapy and post-transplantation care, antiviral prevention, and therapy, cytomegalovirus (CMV) infection remains the most common viral infection after solid organ transplantation (SOT). Methods This study included 2,375 patients under the care of our transplant center during the 1-year period from June 2012 to June 2013. There were 351 patients (14.78%) suspected and tested for CMV infection with the use of viral DNA amplification test. Results Symptoms that triggered diagnostics were graft dysfunction in 24 (55.8%), diarrhea in 18 (41.9%), fever in 15 (34.9%), leukopenia in 14 (32.6%), abdominal pain in 13 (30.2%), nausea in 7 (16.3%), cough in 6 (14%), and shivers in 2 (4.7%). Positive test results were obtained in 43 patients (12.3% of patients tested and 1.8% of the entire cohort). The group consisted of 17 women (39.5%) and 26 men (60.5%), 26 kidney (60.5%) and 17 liver (39.5%) transplant recipients, aged 49.3 years (SD 14.9). The initial viral load was median 8,093 (range: 4,232–219,180) copies/mL. The mean ganciclovir (GCV) treatment duration was 19.05 (SD 8.1) days. GCV doses ranged from 100 to 1,000 mg/d, mean 370.6 (SD 254.2) mg/d. Clinical resistance to treatment was diagnosed in 5 patients (11.6%). We found a positive correlation of GCV treatment duration with natural logarithm of initial CMV viremia (r = 0.56; P = .0002) and of time in months to CMV infection with mean cyclosporine level (r = −0.74; P = .04) and GCV dose (r = −0.34; P = .03). The duration of GCV therapy was positively influenced by CMV load and tacrolimus administration and negatively by patient's age and male sex. Conclusions Appearance of any symptoms occurring after transplantation, even nonspecific, should lead to diagnostics for CMV infection. The duration of treatment depends on the severity of the infection expressed by CMV viremia. Clinical resistance to GCV is not frequent, but it is an important transplantologic problem.