Nicholas DiPaola

Antibodies Reactive to Non-HLA Antigens in Transplant Glomerulopathy

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

An Experimental Model of Acute Humoral Rejection of Renal Allografts Associated with Concomitant Cellular Rejection

Acute humoral rejection (AHR), which occurs in up to 8% of kidney transplant recipients, is a significant cause of renal allograft dysfunction and loss. More efficacious treatment modalities are needed to eliminate or curtail alloantibody production and its deleterious effects on the kidney. The availability of animal models mimicking human AHR is essential to understand its pathophysiology and develop new treatment strategies. Using a mouse kidney transplant model, we demonstrate that presensitization of recipients with donor skin grafts results in rejection of subsequent renal allografts. All presensitized mice developed renal failure 8.6 +/- 4.3 days after engraftment, with serum creatinine values near 100 micromol/dl. Graft histology revealed mild, diffuse, interstitial, mononuclear cell infiltrates; prominent peritubular capillary inflammatory cell margination; patchy interstitial hemorrhage; interstitial edema; and focal glomerular fibrin deposition. Complement (C3d) deposition was diffuse and prominent in peritubular capillaries. Serum analysis demonstrated high levels of circulating alloantibodies with broad cross-reactivity to many MHC haplotypes. The clinical setting and histological findings of our model strongly resemble AHR, which is frequently associated with cellular rejection, a situation commonly encountered in human renal allograft recipients. This animal model provides a valuable tool to study the pathogenesis of AHR, its relationship to cellular alloimmunity, its contribution to graft injury, and the effects of various potential therapeutic interventions.

Absence of HLA-DR1 positivity in 2 familial cases of frontal fibrosing alopecia

eosinophil-predominant infiltration is seen in esophageal biopsy specimens. Various conditions presenting esophageal eosinophilia, including GERD, should be excluded. The present case could not be diagnosed as EoE, because the patient had no apparent symptoms of esophageal dysfunction, although dense eosinophilic infiltration was seen in the esophageal biopsy specimens and the endoscopic features were consistent with EoE. The patient had no other disorders that might cause esophageal eosinophilia, and we cannot completely exclude the possibility that the patient’s condition will progress to EoE in the future. Chemical mediators released from mast cells are well known to induce eosinophilic infiltration. TGF1, which is expressed by both eosinophils and mast cells, has been recognized as an important molecular mediator of EoE. Abonia et al provided evidence for the involvement of KIT ligand in the pathogenesis of EoE. Niranjan et al reported that mast cells play a critical role in muscular cell hyperplasia and possibly in the esophageal

The pathogenesis of acute allograft dysfunction in desensitized renal transplant recipients

Acute allograft rejection after HLA desensitization is common early post‐transplant but the sequence of histopathologic changes leading to graft dysfunction has not been well defined.

Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation

De novo donor‐specific antibodies (dnDSA) post‐transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post‐transplant dnDSA can occur within the first post‐transplant year.

Antibody-mediated rejection in a lung transplant recipient after acute stroke

Antibody-mediated rejection (AMR) is becoming a more recognized problem in lung transplantation. We present a case of late onset AMR in a lung transplant recipient after an acute embolic stroke requiring thrombolytic therapy, who previously had a completely unremarkable course for over 3 years.