Purpose: Humoral allograft rejection is a defined mechanism for cardiac and renal graft dysfunction; C4d deposition, a stable component of complement activation, inversely correlates with graft survival. With the recent recognition of humoral rejection in lung grafts, we examined C4d's role as a prognostic adjunct in lung allografts. Material and Methods: Twenty‐three lung recipients underwent biopsies for deterioration in clinical status or routine surveillance. Clinically unwell patients possessed acute rejection or bronchiolitis obliterans syndrome (BOS). Biopsies attributable to infection were excluded from the study. In addition to routine light microscopy, an attempt was made to correlate the clinical status and morphologic findings with the pattern of C4d deposition and also to compare these clinical and morphologic parameters with the other assessed immunoreactants. Panel reactive antibody testing was also carried out at various points in their post transplantation course whereby in 6 of the cases the samples were procured at exactly the same time as the tissue samples. Results: The patients were segregated into two groups: those patients with recurrent acute rejection and those with BOS. In those patients with symptomatic acute rejection, all biopsies showed light microscopic and immunofluorescent evidence of humoral allograft rejection. The level of C4d was positively correlated with the degree of parenchymal injury, the hallmark being one of septal capillary necrosis. In addition, high and intermediate levels of C4d correlated with a clinical diagnosis of acute rejection. C4d was the strongest predictor of parenchymal injury and of the clinical status (p < .0001) compared to other the immunoreactants C1q, C5b‐9 and immunoglobulin. There was no specific correlation between C4d deposition and the presence of acute cellular rejection. In those patients fulfilling clinical criteria of BOS, deposits of C4d as well as other immunoreactants were found in the bronchial wall as opposed to the rarity of this finding in bon‐BOS patients. However the only statistically significant predictor of BOS was bronchial wall deposition of C1q. In no case were panel reactive antibodies at significant levels discovered post transplantation. Conclusions: In the context of acute rejection, C4d deposition correlates with clinical evidence of rejection and the degree of humoral rejection assessed pathologically; there is no association with the presence of histocompatibility related antibodies. It is a more specific predictor of allograft status compared to other immunoreactants. C4d deposition within the bronchial wall is a feature of BOS and hence may be used as a marker of chronic graft dysfunction. The antigenic target resulting in C4d deposition may not be histocompatibility related.

We have recently recognized humoral rejection (HR) in lung allograft recipients and its association with acute and chronic graft dysfunction. We have shown that C4d, a stable marker of classic complement activation, is deposited in lung allografts, correlating with clinical rejection and parenchymal injury. The antigenic target may be endothelium in the setting of recurrent acute rejection while varying components of the bronchial wall may be important in chronic graft dysfunction. We sought to establish whether there is a role for antibodies with histocompatibility antigen specificity in the lung humoral allograft phenomenon. Flow cytometric and ELISA assays to assess donor-specific antigens were conducted on sera from 25 lung transplant recipients who had experienced one or more episodes of clinical rejection; in addition, the serum samples were tested for evidence of antiendothelial cell antibody activity. Morphologically, each case had biopsies showing septal capillary injury with significant deposits of immunoreactants with microvascular localization and positive indirect immunofluorescent antiendothelial cell antibody assay. Panel-reactive antibody testing showed absence of MHC Class I/II alloantibodies; ELISA based crossmatch detecting donor-specific MHC Class I/II specific antibodies was negative. HR can occur in the absence of antibodies with HLA specificity; antigenic targets may be of endothelial cell origin.

Immunocytomas represent low grade B cell lymphomas related to marginal zone lymphoma but with a predominance of cells having plasmacytic features. Eleven patients presented with lesions compatible with primary cutaneous immunocytoma. The expression of CD2, CD3, CD5, CD20, CD21, CD23, CD43, CD56, CD79, and bcl-2 was analyzed immunohistochemically and of lambda and kappa light chains by an in situ hybridization assay. There were 6 men and 5 women ranging in age from 43 to 76 years. The most common clinical presentation was as extremity based clustered erythematous brown papules. Therapy with local irradiation or Rituximab resulted in lesional resolution. Underlying illnesses included Sjögren's syndrome, hepatitis C, ulcerative colitis, autoimmune thyroid disease, and rheumatoid arthritis. Four patients were taking medications previously associated with immune dysregulation. In two patients in whom a paraproteinemia was uncovered. The most common pattern light microscopically was perivascular small lymphocytic and plasmacellular infiltrates mimicking architecturally a reactive process. Phenotypic studies revealed a marginal zone (MZL) phenotype amid the small atypical lymphocytic infiltrate and highlighted a reactive background population of non-neoplastic T and B cells; light chain restriction was seen amid the plasma cells. In one case there was EBER staining of plasma cells while in another case in whom there was hepatitis C seropositivity staining of plasma cells for hepatitis C associated RNA transcripts was observed. Primary cutaneous immunocytoma appears to arise from a pre-existing state of reactive lymphoid hyperplasia. latrogenic and endogenous immune dysregulation including in the context of lymphotropic viral infections is implicated.