Impact of COVID-19 pandemic on transplant laboratories: How to mitigate?

A positive flow cytometry crossmatch (FCXM) due to donor specific antibodies (DSA) constitutes a risk for kidney transplantation; such a finding may indicates an unacceptable donor for this patient. However, positive FCXM in the absence of DSA is considered discordant and need further investigations. During COVID-19 pandemic, we observed 22% discordant results out of 445 FCXM performed during eight months period in our laboratory and another 7% were invalid due to high background negative control (NC). No study has addressed the impact of COVID-19 pandemic on FCXM and the overall pre-kidney transplant workups or described a solution to deal with these non-specific reactivities. Herein, we analyzed all FCXM results in SARS-CoV-2 seropositive patients and addressed how this pandemic affected significantly the pre-kidney transplant workups, highlighting both technical and financial implications. We also shared our modified FCXM procedures using dithiotheritol (DTT) sera treatment or blocking donor cells with negative control human serum (NCS) which we found to be successful to abrogate 98% of all discordant FCXM results and to validate all invalid results due to high background NC. In conclusion, COVID-19 pandemic has affected our HLA laboratory significantly by creating many false positive or invalid crossmatch results. Transplant laboratories must consider this before test interpretations and immune risk assessments. We recommend the use of DTT serum treatment to remove nonspecific bindings in the sera of kidney transplant candidates and the use of NCS-blocked donor cells to correct high background when performing FCXM in transplant candidates or donors with recent history of SARS-CoV-2 immunization respectively.

Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.

BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

The novel allele, HLA-A*32:148, identified by next generation sequencing in a Saudi individual.

A single nucleotide substitution in exon 4 of HLA-A*32:01:01:01 results in novel HLA-A*32:148 allele.

How common is celiac disease in Eastern Saudi Arabia?

BACKGROUND: In contrast to its prevalence in Europe, celiac disease (CD) is considered rare in non-Caucasian populations. We aimed to estimate the prevalence of CD in clinically suspicious celiac disease patients and in patients with disorders known to be associated with CD, such as autoimmune diseases, using serological assay for IgA-endomysial antibodies (EMA) on inexpensive human tissue substrate. PATIENTS AND METHODS: IgA-endomysial and IgA-reticulin antibodies (ARA) were evaluated by indirect immunofluorescence (IIF) study using human umbilical cord (HUC) and rat tissues, respectively, in the following groups: group 1, 145 patients with clinical suspicion of CD; group 2, 80 with autoimmune diseases; group 3, 20 patients with inflammatory bowel disease (IBD); and group 4, 100 healthy blood donors. RESULTS: Of the 145 patients with suspected CD (group 1), 11 were EMA positive with or without ARA, giving a serological prevalence of 7.6%. The histological findings of intestinal biopsy were confirmed in six of them, indicating a CD prevalence of 4%. In group 2, two EMA-positive (2.5%) with or without ARA cases were found. Both were from the 18 patients who had autoimmune thyroid disease, indicating an 11% prevalence of EMA in autoimmune thyroid disease. No positive EMA was detected in the 3rd and 4th groups, indicating 100% specificity. CONCLUSION: Our findings showed high prevalence of CD in a reference laboratory setting. This highlights the importance of keeping CD in mind and of promptly investigating suspected individuals. There is also a high prevalence of CD among patients with autoimmune thyroid diseases, and further studies are needed to elucidate the significance of this association. Test for endomysial antibodies using human umbilical cord is an inexpensive, easily available and highly specific tool for identifying patients to undergo biopsy and to screen at-risk groups of patients.