Renal Transplant in a Fully Human Leukocyte Antigen Matched Parent-child – A Case Report

Dear Editor, I am writing to present a compelling and rare case report titled "Complete human leukocyte antigen (HLA) matching in renal transplantation due to consanguinity," which we believe holds significant clinical and research implications in the field of organ transplantation. Our case underscores the role of consanguineous marriages in shaping HLA compatibility and its impact on transplant outcomes. The HLA system, also known as major histocompatibility complex, are polymorphic protein complexes, encoded by the short arm of chromosome six. They are primarily involved in immune regulation, and by extension are the one of the most important players of rejection. The HLA gene is inherited in a codominant fashion from both parents, and thus, the HLA studies within a family of four (mother, father, and two children) reveal that the two siblings have a 25% chance of being HLA identical, 50% chance of being HLA haploidentical, and 25% chance of sharing no HLA haplotypes.[1] In rare cases, consanguineous marriages through multiple generations lead to a complete HLA matching between siblings/parents due to shared alleles between the parents. Here, we present a case of a mother–son, with 100% HLA match identified before transplantation. Our patient was a 20-year-old male, born out of consanguineous marriage, full-term normal delivery with normal developmental milestones. The patient was apparently normal until 2 years back, and then, he was diagnosed as chronic kidney disease and started on hemodialysis. The patient presented with breathlessness and volume overload. There was no history of renal stones or lower urinary tract symptoms. There was no history of renal disease in the family. His mother was ABO compatible and was willing to be donor for renal transplant. Hence, the mother–son were worked up for renal transplant. During HLA testing done by SSOP technique, the HLA profile of the recipient (son) was HLA A*11 A11 HLA B*51 51 HLA Cw*14 14 HLA DRB1*08 08 HLA DQB*03 03. The HLA profile of the prospective donor (mother) was HLA A*11 A11 HLA B*51 51 HLA Cw*14 14 HLA DRB1*08 08 HLA DQB*03 03. The donor and the recipient had a 100% HLA match (mother and son). Table 1 shows the HLA profile of the mother and son. The profile was repeated, and it yielded a similar result. Further history revealed multiple consanguineous marriages that had happened over generations. The pedigree chart of the family is given in Figure 1. The parents had a second-degree consanguineous marriage. The grandparents were not related; however, the great grandparents had a second-degree consanguineous marriage. Renal transplant was done without any induction. The patient was put on triple immunosuppression including tacrolimus 0.1 mg/kg in two divided doses, mycophenolate mofetil (MMF) 1 g in two divided doses and prednisolone at 0.5 mg/kg. The patient had immediate graft function. The posttransplant period was uneventful. The patient was discharged on postoperative day 10 with an output of 3480 ml and creatinine of 1.2. The patient is on regular follow-up with tacrolimus 2 mg twice daily MMF 500 mg twice daily and prednisolone 10 mg.Figure 1: Pedigree chart showing the consanguinity in various generations in the familyTable 1: Human leukocyte antigen profile of the patient and donorThe worldwide prevalence of consanguineous marriages is around 10%. It is widely practiced in Middle East, Africa, and South Asian countries. A 2015–2016 nationwide survey puts the incidence at around 16%. The incidence was 3 times more in South India compared to North India. The most common consanguineous marriage practiced in India is a first cousin marriage as in our case.[2] In Saudi Arabia, an analysis to find a fully HLA-matched donor for a hematopoietic stem cell transplant found that 22% of patients had a fully HLA-matched parent. Ten percent of patients had a full HLA-matched mother. This high incidence was attributed to the high degree of consanguineous marriages in Saudi, which is among the highest in the world.[3] Another case report from Bahrain reported a family of six (father, mother two daughters and son) with both sons who were 100% matched with the mother and one daughter who was 100% matched with her father. The parents had a 50% HLA match.[4] However, no such case reports are mentioned in the Indian literature as far as our knowledge is concerned. In our case, there was a history of consanguinity through multiple generations that probably lead to 50% matched parents and thus leading to a 100% matched mother and child. Another important clue was the mother had identical haplotypes of HLA (HLA A*11 A11 HLA B*51 51 HLA Cw*14 14 HLA DRB1*08 08 HLA DQB*03 03) suggesting she inherited similar haplotypes from both her parents. A possible mode of inheritance is described in Figure 2.Figure 2: Possible mode of inheritance of human leukocyte antigen alleles in this familyIn a 2015 study on HLA haplotype distribution showed the prevalence of HLA A*11 and B*51 was 13% and 8%, respectively.[5] In a 2022 study of HLA DRB and DQB profile in three ethnic Tamil groups, the incidence of DRB1*08 was 0.45% and DQB*03 was around 11%–15%.[6] HLA compatible donors was associated with better 3 years survival than HLA incompatible donors.[7] Also such individuals could be considered of low immunological risk and an early steroid withdrawal protocol/steroid minimization/steroid free regimen is also an option, to avert steroid related side effects. The median glomerular filtration rate does not significantly differ, and there is a reduced risk of posttransplant diabetes mellitus and dyslipidemia. However, there is an increased risk of acute rejection in steroid-free/steroid withdrawal regimen.[8,9] Barbari et al. showed that more consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their nonconsanguineous counter-parts in Lebanon (45% vs. 33%, P < 0.02 and 42% vs. 27%, P < 0.01), respectively.[10] The incidence of genetic kidney diseases is increased in consanguineous marriage.[11] However, there is no large multicenter data on consanguinity as a risk factor for chronic kidney disease. In this case, the etiology of renal disease is unknown. However, there was no family history of renal disease. Hence, genetic testing was not done in this case. The patient's family would not cooperate for an HLA testing of the siblings and the father and hence a complete HLA mapping of the family could not be done. Complete HLA-matched parent–child remains a rarity in medical literature even though it could be fairly common in certain regions. With respect to our results, we can conclude that in societies with higher prevalence of consanguineous marriages, the incidence of complete HLA matching might be higher, and with further testing, such unique cases can be identified and their response to renal transplantation can be better understood. Declaration of patient consent The patient consent has been taken for participation in the study and for publication of clinical details and images. The patient understands that the name and initials would not be published, and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.