RESUMEN
Objective: To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection. METHODS: The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20. RESULTS: Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037). Conclusion: Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.
Asunto(s)
COVID-19 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Subgrupos Linfocitarios , Recuento de Linfocitos , Biomarcadores , Citocinas , Gravedad del PacienteRESUMEN
OBJECTIVES: Plasma cell-rich acute rejection is an aggressive form of acute rejection that occurs late after transplant and is usually resistant to standard antirejection therapy. This study reports the safety, efficacy, and outcomes of plasma cell-rich acute rejection after treatment with bortezomib, a proteasome inhibitor, in 10 patients after a first living-related renal transplant. MATERIALS AND METHODS: Plasma cell-rich acute rejection was diagnosed using the 2007 Banff classification. The treatment protocol for plasma cell-rich acute rejection included methylprednisolone (500 mg/kg), 7 sessions of plasmapheresis, antithymocyte globulin (3-5 mg/kg/day for 10 days), rituximab (2 doses at 375 mg/m2), and bortezomib (1 cycle at 1.3 mg/m2). RESULTS: The mean age of recipients and donors was 23.70 ± 11.39 and 37.30 ± 12.82 years, respectively. The mean time to plasma cell-rich acute rejection was 3.1 ± 2.5 years. The mean serum creatinine level at rejection was 4.8 ± 2.7 mg/dL. After treatment, serum creatinine decreased to 3.3 ± 1.8 mg/dL. Serum creatinine levels at 1-year and 2-year follow-up were 3.0 ± 2.3 and 3.3 ± 0.9 mg/dL, respectively. There was 1 graft failure due to recurrence of glomerulonephritis/de novo glomerulonephritis. No significant adverse effects were noted in the patients. Bortezomib successfully reverted plasma cell-rich acute rejection and stabilized graft function, with patients showing 2-year graft survival after rejection of 90%. CONCLUSION: Bortezomib-based treatment was successful in reverting plasma cell-rich acute rejection and stabilizing graft function, with graft survival of 90% at 2 years. Further studies with large cohorts and randomized trials with or without bortezomib will help in better evaluation of its efficacy, safety, and outcomes.