Introduction It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), ...surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions. Methods Using polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. Results We confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection (recipient age range at the time of transplant: 1-9 years, median: 2 years) revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in deceased adult donors. In available pan-scope biopsies from pediatric recipients, we observed higher percentages of naïve recipient B cells in colon allograft compared to small bowel allograft and increased BCR overlap between native colon vs colon allograft compared to that between native colon vs ileum allograft in most cases, suggesting differential clonal distribution in large intestine vs small intestine. Discussion Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of stabilization of the mucosal B cell repertoire in pediatric ITx patients.
Valgus knee deformities pose a unique challenge in total knee arthroplasty (TKA) due to the complexity of achieving ligamentous balance and satisfactory alignment compared to varus or neutral ...deformities. Robotic-assisted (RA) TKA could aid in achieving improved component alignment and balance.
We retrospectively evaluated a matched cohort of patients to compare image-free RA-TKA (n = 44) versus conventional manual (CM) TKA (n = 30) techniques in patients who have valgus deformity of 5 to 15 degrees, including radiographic and patient-reported outcomes measures (PROMs) over a 3-year period. The patient reported outcome measures (PROMs) studied to determine outcomes were: Western Ontario McMaster University Arthritis Index, Knee Society Score-Function Score, and Short Form 12-item Survey.
Overall, the RA-TKA cohort showed faster improvement in PROMs (37.16 ± 1 8.8 versus 25.74 ± 17.7, P = .02), shorter length of stay (1.41 versus 2.29 days, P = .02), and shorter operating room times (120.79 versus 123.67 minutes, P = .02) than CM-TK). Additionally, there was no difference in the use of primary versus varus-valgus constrained polyethylene liners between the cohorts.
In this investigation, RA-TKA yielded a slightly faster patient recovery, more objective measurements of ligamentous balance, and proved noninferior PROMs compared to CM-TKA for preoperative valgus knee deformities.
Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues.
By applying flow cytometry and next generation ...sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels.
Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire.
Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool.
This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
Background: Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. Methods: By applying flow cytometry and ...next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. Findings: Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. Interpretation: Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. Funding: This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
The anterior-based muscle-sparing (ABMS) approach, using the intramuscular interval between the tensor fascia lata and gluteus medius, is an increasingly popular total hip arthroplasty (THA) ...approach. Its incidence of lateral femoral cutaneous nerve (LFCN) numbness has not been defined. The incidence of LFCN symptoms in direct anterior THA ranges from 7%-32% at 1-year follow-up1-4. The purpose of this study is to determine the incidence of LFCN symptoms in patients who underwent ABMS THA at 1-year follow-up.
This was a single-center, multisurgeon retrospective study of ABMS THAs with minimum 1-year follow-up data between January 2014 and September 2021. Eight hundred sixty-nine THAs were included. Mean age of the patients was 67.2 years, with 43.4% male and 56.5% female. Mean body mass index was 26.8, and mean American Society of Anesthesiologists was 2.3. Statistical analysis included chi-square tests, 2-sample t-test, and binomial logistic regression. A P-value of .05 was considered statistically significant for all tests.
Nine patients (1%) reported LFCN-associated symptoms at 1-year follow-up. The most common complaint was numbness (n = 5, 55.6%), followed by diminished sensation (n = 2, 22.2%), burning (n = 1, 11.1%), and generalized pain (11.1%). There was no difference in age, sex, body mass index, or American Society of Anesthesiologists between the group that experienced symptoms and the group that did not (P = 1.00, P = .34, P = .74, P = .80).
The incidence of LFCN dysfunction is 1% at 1 year after surgery with the ABMS approach. Additional studies may elucidate all risks and benefits of the ABMS approach with respect to LFCN injuries.
