ABSTRACT
Allergic rhinosinusitis involves several types of inflammatory cells. The dominant inflammatory cells include mast cells, eosinophils, lymphocytes, and monocytes/macrophages. Since eosinophils are one type of inflammatory cell that is often related to allergy, we investigated in this study whether the eosinophils present in rhinosinusitis may be potential targets for CD52 antibody treatment. First, we found that circulating eosinophils in renal recipients were almost completely depleted after iv bolus of treatment with Campath-1H, a humanized antibody against CD52 antigen. Second, we showed morphologically that eosinophils, lymphocytes, and monocytes gave positive staining reactions for CD52. Third, using an automated clinical imaging system, we found that tissue sections of sinus contents with prominent eosinophils (eosinophilic rhinosinusitis) yielded significantly higher CD52 staining scores than those with lymphocytes as the dominant component (lymphocytic rhinosinusitis). These findings indirectly support the hypothesis that CD52 may be a target for treating eosinophilic rhinosinusitis with Campath 1H.
Subject(s)
Antigens, CD/metabolism , Antigens, Neoplasm/metabolism , Eosinophils/metabolism , Glycoproteins/metabolism , Rhinitis/metabolism , Sinusitis/metabolism , Adult , Alemtuzumab , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/therapeutic use , Antigens, CD/immunology , Antigens, Neoplasm/immunology , Biomarkers/metabolism , CD52 Antigen , Eosinophils/immunology , Eosinophils/pathology , Female , Glycoproteins/immunology , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Rhinitis/immunology , Rhinitis/pathology , Sinusitis/immunology , Sinusitis/pathology , Tissue Array AnalysisABSTRACT
We report 2 complicated cases of thrombotic microangiopathy with chronic features and active components. The first case was a 36-yr-old woman with positive anti-DNA antibody and possible lupus cerebritis, who developed thrombotic microangiopathy secondary to a series of syndromes, including preeclampsia and anti-phospholipid antibody syndrome. Renal biopsy revealed no evidence of lupus nephritis and her renal function returned to normal 1 week after the biopsy. The second case was a 46-yr-old man who developed thrombotic microangiopathy of unknown etiology, which led to end-stage renal disease within 6 mo. The patient received a living related-donor transplant, but thrombotic microangiopathy recurred in the donor kidney only 40 days after the renal transplantation.
Subject(s)
Kidney Transplantation , Kidney/blood supply , Pregnancy Complications, Cardiovascular , Thrombosis/complications , Adult , Antiphospholipid Syndrome/complications , Chronic Disease , Female , Glomerular Basement Membrane/pathology , Humans , Kidney/pathology , Kidney Failure, Chronic/etiology , Kidney Transplantation/pathology , Male , Microcirculation , Middle Aged , Pregnancy , Thrombocytopenia/etiologyABSTRACT
Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.
Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Neoplasm/pharmacology , Graft Rejection/prevention & control , Kidney Transplantation , Monocytes/drug effects , Adolescent , Adult , Aged , Alemtuzumab , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/immunology , Antigens, CD/immunology , Antigens, Neoplasm/immunology , CD52 Antigen , Female , Glycoproteins/immunology , Humans , Kidney/drug effects , Kidney/pathology , Male , Middle AgedABSTRACT
Campath-1H (alemtuzumab), a humanized monoclonal antibody against CD52, can cause more profound depletion of lymphocytes than monocytes. The resultant imbalance of lymphocytes and monocytes after Campath-1H treatment of a renal-transplant recipient may lead to an acute rejection dominated by monocytes. We report such a case of acute transplant rejection in a 49-yr-old man who received a living non-related kidney transplant and was treated with preoperative Campath-1H and postoperative immunosuppression. An initial post-transplant renal biopsy showed diffuse mild acute rejection with 95% CD68-positive monocytes, but only 5% CD3-positive T lymphocytes. Inflammatory cells in the renal biopsy were negative for CD34 and CD1a stains, suggesting non-involvement of CD34-derived dendritic cells in the acute rejection. After steroid treatment for 2 wk, the patient's serum creatinine concentration diminished to 1.5 mg/dl. The histopathological features of acute rejection were absent in a second biopsy of the transplanted kidney. In summary, this case is an instance of monocyte-mediated acute rejection of a transplanted kidney.
