Persistent T-Cell Reactivity in a Seronegative Patient after SARS-CoV-2 Infection and One Vaccination

We present here a 64-year-old male participant of the CoNAN study who experienced a PCR-confirmed mild SARS-CoV-2 infection but did not develop any measurable antibody response. Additionally, after vaccination with ChAdOx1 (AstraZeneca, Cambridge, UK) 11 months later, no antibodies were detected in six serological tests three weeks after the vaccination. When we assessed T-helper (Th) cell immunity, SARS-CoV-2-specific Th cells produced detectable amounts of IFNγ and TNF six weeks after the infection. A robust T-cell immunity remained detectable at least until six months after the infection and was boosted by the vaccination thereafter. This case report points out that an assessment of a prior infection or a vaccine response based solely on antibody detection might have limitations in individual patients.

Emergence of Letermovir-resistant HCMV UL56 mutant during rescue treatment in a liver transplant recipient with ganciclovir-resistant infection HCMV: a case report

Background Human Cytomegalovirus (HCMV) still represents a crucial concern in solid organ transplant recipients (SOTRs) and the use of antiviral therapy are limited by side effects and the selection of viral mutations conferring antiviral drug resistance. Case presentation Here we reported the case of an HCMV seronegative patient with common variable immunodeficiency (CVID), multiple hepatic adenomatosis, hepatopulmonary syndrome and portal hypertension who received a liver transplant from an HCMV seropositive donor. The patient was treated with Valganciclovir (vGCV) and then IV Ganciclovir (GCV) at 5 week post-transplant for uncontrolled HCMV DNAemia. However, since mutation A594V in UL97 gene conferring resistance to ganciclovir was reported, GCV therapy was interrupted. Due to the high toxicity of Foscarnet (FOS) and Cidofovir (CDV), Letermovir (LMV) monotherapy at the dosage of 480 mg per day was administered, with a gradual viral load reduction. However, a relapse of HCMV DNAemia revealed the presence of mutation C325Y in HCMV UL56 gene conferring resistance to LMV. Conclusions In conclusion, even if LMV is an effective and favorable safety molecule it might have a lower genetic barrier to resistance. A warning on the use of LMV monotherapy as rescue treatments for HCMV GCV-resistant infections in transplant recipients is warranted.

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA (“seropositive”) in general display a different etiology and disease course compared to so-called “seronegative” patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.

Fatal donor-derived Kaposi sarcoma following liver transplantation

Human herpesvirus-8 (HHV8) is a recognised precursor for a number of neoplastic and non-neoplastic processes. Immunosuppressed recipients of both solid organ and haematopoietic stem cell transplants are at risk of life-threatening lytic reactivations of HHV8-infected B-lymphocytes, primary infections after receiving grafts from HHV8-seropositive donors and more rarely by the direct transplantation of malignant Kaposi sarcoma cells seeded within graft tissue. We describe the case of an HHV8-seronegative patient with confirmed, post-orthotopic liver transplant transmission of HHV8 from a seropositive donor with quantitative evidence of viraemia and subsequent development of disseminated visceral and cutaneous Kaposi sarcoma with a rapidly fatal outcome.

A57 THE USE AND INTERPRETATION OF HLA-DQ2/DQ8 GENOTYPING BY PEDIATRIC GASTROENTEROLOGISTS

Background A recent classification of high and low risk alleles associated with celiac disease (CD) shows that the presence of a single allele (DQA1*05 or DQB1*02; coding together for HLA-DQ2), without a positive genotype (HLA-DQ2 and or HLA-DQ8), represents a risk of developing the disease. Aims The aim of this study is to evaluate the use and interpretation of the HLA-DQ2/DQ8 genotyping by pediatric gastroenterologists, as there is no study on the matter and the latest guidelines do not address this risk classification. Methods A web-based survey was sent by email to all NASPGHAN (North American society of pediatric gastroenterolgy, hepatology and nutrition) members. Results Results 294 pediatric gastroenterologists sent a complete survey. 86,1% use the HLA-DQ2/DQ8 genotyping according mainly to the NASPGHAN and ESPGHAN guidelines. The main indications considered were to exclude CD in a patient on a gluten-free diet with a resolution of his symptoms and in a seronegative patient with equivocal biopsies. A minority would consider the genotyping for screening high risk groups or for making a diagnosis in children with high specific CD antibodies and strong clinical suspicion without performing biopsies, as suggested by the ESPGHAN guidelines. The alleles associated with CD are not well known, but 76,7% the participants are aware of the risk classification. While only 62,8% have access to the complete genotype, 47,8% consider it useful. Nevertheless, 82,6% would still want to know the presence of a low risk allele. Conclusions The risk classification of alleles related to CD warrants a modification of the genotyping result with access to the alleles and an adaptation of the guidelines. Funding Agencies None