Follow-up of Immune Response in Patients with Common Variable Immunodeficiency following SARS-CoV-2 Vaccination.

The COVID-19 pandemic highlighted the importance of effective vaccination strategies in controlling the spread of infectious diseases. SARS-CoV-2 vaccine has demonstrated high efficacy in preventing COVID-19 infection in the general population. However, the efficacy of this vaccine in patients with predominantly antibody deficiencies, such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA), should be closely monitored. CVID and XLA are rare genetic disorders that impair the immune system's ability to produce antibodies, which are crucial for fighting infections. Patients with these disorders have a higher risk of severe disease and mortality from COVID-19 due to their compromised immune systems. In this study, we evaluated the humoral and cellular immune responses after four doses of mRNA-1273 and one BNT162b2 bivalent vaccine in a cohort of patients with CVID and XLA. The response in this population was lower than in the control group. However, the administration of the third dose improved the number of patients with seroconversion and the intensity of the humoral response, as well as the number of patients with a positive cellular response. Finally, the administration of the fourth and fifth doses improves the antibody titer and neutralization against wild type variant, but not against the prevalent XBB1.5 variant.

Comparison of an Enzyme Linked-Immunosorbent Assay and a Chemiluminescent Immunoassay with an Immunofluorescence Assay for Detection of Phase II IgM and IgG Antibodies to Coxiella burnetii.

In this study, we have compared the detection of IgM and IgG against C. burnetii phase II of an enzyme-linked immunosorbent assay (ELISA) (Euroimmun) and a chemiluminescent immunoassay (CLIA) (VIRCLIA, Vircell). In addition, an indirect immunofluorescence assay (IFA) was used as a reference test. One hundred forty-eight sera were used for IgG evaluation, and eighty-eight for IgM. The sensitivity of ELISA and CLIA in detecting phase II IgM was excellent. On the other hand, the CLIA IgM showed better specificity than the ELISA IgM. As for phase II IgG, the specificity of ELISA and CLIA was similar, while the ELISA technique showed a higher sensitivity. In conclusion, the best system to detect phase II IgM antibodies against C. burnetii is the CLIA from Vircell, which is characterized by high sensitivity and specificity. For the detection of phase II IgG, the Euroimmun ELISA and Vircell CLIA assays are suitable for the determination of this marker in the laboratory, although the IgG ELISA has greater sensitivity.

Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation.

BACKGROUND: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. METHODS: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. RESULTS: dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. CONCLUSIONS: Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.

Incidence, Management Experience and Characteristics of Patients with Giardiasis and Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is an antibody immunodeficiency with a wide variety of clinical and immunological manifestations, and whose genetic cause is found in about 25% of diagnosed cases. Giardia lamblia is one of the main causes of gastrointestinal infections in CVID. 5-Nitroimidazoles are the most used first-line treatment, but nitroimidazole-refractory giardiasis is increasing. Nevertheless, only a few cases of refractory giardiasis in CVID have been reported. This study aimed to determine the incidence of Giardia infection in our CVID cohort, shows our management experience and describes patients' phenotypic features. Clinical data collection, immunological, immunogenetics and microbiology assays were performed, and previous cases of giardiasis in CVID were reviewed. The incidence of symptomatic giardiasis was 12.9%. The main immunological features were undetectable or decreased IgA levels and reduced switched memory B cells. A probable PTEN pathogenic variant was detected in one. Three patients responded to metronidazole but suffered reinfections, and one was a refractory giardiasis eradicated with innovative quinacrine plus paromomycin combination. This work could contribute to the decision-making and therapeutic management of future patients with CVID and giardiasis, highlighting the importance of the early detection and treatment of infections in patients with CVID to ensure a good quality of life.

Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.

The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.

HLA Class II Polymorphism and Humoral Immunity Induced by the SARS-CoV-2 mRNA-1273 Vaccine.

The vaccines designed against the SARS-CoV-2 coronavirus are based on the spike (S) protein. Processing of the S protein by antigen-presenting cells (APC) and its subsequent presentation to T cells is an essential part of the development of a humoral response. HLA-class II alleles are considered immune response genes because their codified molecules, expressed on the surface of APCs (macrophages, dendritic, and B cells) present antigenic peptides to T cell via their T cell receptor (TCR). The HLA-class II genes are highly polymorphic, regulating what specific peptides induce follicular helper T cells (TFH) and promote B lymphocyte differentiation into plasma or memory B cells. This work hypothesizes that the presence of certain HLA-class II alleles could be associated with the intensity of the humoral response (amount, length) to the SARS-CoV2 mRNA 1273 vaccine. We have studied the relationship between the HLA-class II typing of 87 health workers and the level of antibodies produced 30 days after vaccination. We show a possible association between the HLA-DRB1* 07:01 allele and the HLA-DRB1*07:01~DQA1*02:01~DQB1*02:02 haplotype to a higher production of antibodies 30 days after the administration of the second dose of mRNA-1273.

Study of humoral and cellular immunity in vaccinated with mRNA-1273.

The new vaccines against SARS-CoV-2 have raised a lot of expectations about their ability to induce immunity and the duration of this. This is the case of mRNA vaccines such as Moderna's mRNA-1273. Therefore, it is necessary to study the humoral and cellular immunity generated by these vaccines. Our objectives are determining what is the normal response of antibody production, and what is the level of protective antibodies and monitoring patients in case of subsequent infection with COVID-19. We present the first results of a longitudinal study of the humoral response in 601 health workers vaccinated with Moderna. The results show a humoral immunity at 90 days after the second dose of 100%, with a strong decrease between the levels of circulating anti-S IgG antibodies between days 30 and 90 post-vaccination. Observing a steeper decline in those who had higher titles at the beginning. In addition, we present a cellular response of 86% at three months after the second dose, which is related to low humoral response.

Comparative evaluation of chemiluminescent immunoassay and enzyme-linked immunosorbent assays for the diagnosis of West Nile virus infections.

In August 2020, anew West Nile virus (WNV) outbreak affected 71 people with meningoencephalitis in Andalusia (Spain). Samples from these individuals were received in our laboratory, a regional Virus Referral Centre. The aim of this study was to compare the agreement, sensitivity and specificity of findings between the WNV VIRCLIA IgG and IgM assay (Vircell, Spain) and the WNV ELISA IgM and IgG assay (Euroimmun, Germany) and to compare the performance of WNV VIRCLIA IgM and Euroimmun ELISA for cerebrospinal fluid (CSF) diagnosis. The study included 24 CSF samples (paired with serum samples) and 247 serum samples from 217 patients with suspected WNV infection (1 or 2 per patient). The agreement between ELISA and CLIA tests for IgM and Ig G detection in serum was 93% (kappa index = 0.85) and 96% (kappa index = 0.89) respectively. Sensitivity values of ELISA and CLIA tests for IgM in serum samples were 96.7% and 98.9%, respectively, and specificity values were 96.4% and 95.4% respectively. Sensitivity values of ELISA and CLIA test for IgG in serum samples were 91.1% and 97%, respectively, and specificity values were 100% and 98.8% respectively. Results obtained with ELISA and CLIA tests in CSF samples showed 75% agreement between them (kappa index = 0.51). According to these findings, the WNV VIRCLIA IgM and IgG monotest offers an accurate qualitative detection of WNV in serum and CSF specimens.

Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients.

BACKGROUND: Human leukocyte antigen (HLA) plays an important role in immune responses to infections, especially in the development of acquired immunity. Given the high degree of polymorphisms that HLA molecules present, some will be more or less effective in controlling SARS-CoV-2 infection. We wanted to analyze whether certain polymorphisms may be involved in the protection or susceptibility to COVID-19. METHODS: We studied the polymorphisms in HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and HLA-DQB1) molecules in 450 patients who required hospitalization for COVID-19, creating one of the largest HLA-typed patient cohort to date. RESULTS: Our results show that there is no relationship between HLA polymorphisms or haplotypes and susceptibility or protection to COVID-19. CONCLUSION: Our results may contribute to resolve the contradictory data on the role of HLA polymorphisms in COVID-19 infection.

Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities.

Kidney transplantation, like other transplants, has the risk of producing graft rejection due to genetic differences between donor and recipient. The three known types of renal rejection are listed in the Banff classification: T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mixed rejection. The human leukocyte antigens (HLA) are highly polymorphic and may be the targets of donor-specific antibodies, resulting in ABMR. Therefore, prior to transplantation, it is necessary to analyze the HLA genotype of the donor and recipient, as well as the presence of DSA, in order to avoid hyperacute rejection. However, due to the shortage of kidneys, it is very difficult to find a donor and a recipient with completely matched HLA genotypes. This can trigger a future rejection of the kidney, as is reported in this work. We describe a patient who received a kidney transplant after a negative DSA test, who developed graft rejection with antibodies against the donor's HLA-Bw4 public epitope and lymphocytic infiltrate four days after transplantation, whose differential diagnosis was mixed rejection.

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset.

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.