3D analysis of CROMER (DAF) and a new antigen CRAG.

BACKGROUND: Cromer antigens are carried on decay accelerating factor (DAF, CD55), for which the crystal structure is available. We investigated two samples with an unidentified antibody to a high prevalence antigen and evaluate the location and characteristics of amino acids associated with antigens on the CD55 by 3D modelling. MATERIALS AND METHODS: Antigen typing and antibody identification were by standard methods. CD55 was sequenced, and Cromer variants were generated using the protein's crystal structure (1OK3, chain A). Antigen-associated residues and intraprotein interactions were investigated in 3D (Naccess, Protein Interactions Calculator). RESULTS: The antibody in the sample from a woman of Kashmiri descent was identified as anti-IFC (anti-CROM7). Her RBCs were negative for high-prevalence Cromer antigens including IFC. CD55 sequencing revealed a silent c.147G>A (p.Leu49=) and c.148G>T (p.Glu50Ter) changes, designated CROM*01N.05. The antibody in the sample from a woman of Greek ancestry was only compatible with IFC- RBCs but her RBCs were positive for known high-prevalence Cromer antigens. CD55 sequencing found she was homozygous for c.173A>G (p.Asp58Gly). The high prevalence antigen was named CRAG (ISBT CROM18 or 021018) and the allele designated CROM*01.-18. By 3D analysis, all known antigen-associated residues, including the new CRAG antigen, were exposed at the protein surface. Interactions between antigen-associated residues within the same CD55 domains were identified. DISCUSSION: Identification of antibodies to high prevalence Cromer antigens can be challenging. The surface exposure of antigen-associated residues likely accounts for their immunogenicity. 3D analysis of CD55 provides insight into previous serologic observations regarding the influence of some Cromer antigens on the expression of others.

Acute fibrinous organising pneumonia: a manifestation of trimethoprim-sulfamethoxazole pulmonary toxicity.

A 50-year-old man was treated with trimethoprim-sulfamethoxazole (TMP-SMX) for acute arthritis of his right big toe. Within a few days, he developed dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. Symptoms improved with discontinuation of the antibiotic but worsened again with its reintroduction. An open lung biopsy was performed. We describe the workup performed and the factors that pointed to a final diagnosis of TMP-SMX-related pulmonary toxicity in the form of acute fibrinous organising pneumonia.

Emergency ABO-incompatible liver transplant secondary to fulminant hepatic failure: outcome, role of TPE and review of the literature.

The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO-incompatibility. However, these transplantations are complicated by pre-existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO-incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O-positive with an initial anti-B titer of 64 and the cadaveric organ was from a B-positive donor. The patient underwent initial TPE during the peri-operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody-mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti-B titer was reduced and maintained at 8 or less 8 months post-op. However, an elevation of transaminases 3 months post-transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO-incompatible liver transplant.

The rise of cellular therapy.

In 1938, the field of Transfusion Medicine began as the simpler entity - Blood Banking. It was a discipline that focused on collecting, processing, storing and distributing end stage blood cells, plasma and plasma fractions to patients. Over the years, the field progressed to include clinical patient services such as apheresis technology and with the development of stem cell transplantation as a standard of care, Cell Therapy. Now the discipline is also finding a niche in the area of Regenerative Medicine. The role played by Transfusion Medicine practitioners in Cell Therapy and Regenerative Medicine was predicated on many factors: (1) pre-existing, established protocols for therapeutic leukapheresis, (2) prior experience with mononuclear cell collection and processing, (3) long term familiarity with, and a clear understanding of, cGMP and cGLP guidelines, Federal regulations, and the voluntary standards established by various organizations, (4) close relationships with practitioners in clinical departments of medicine, pediatrics, oncology, surgery, and their subspecialty areas. While the initial Cell Therapy programs related primarily to hematopoietic stem cell transplantation, as Regenerative Medicine programs developed, transfusion specialists found it to be a related field that would also benefit from their input. Cell Therapy and Regenerative Medicine, now provide fertile soil for the seeds of Transfusion Medicine to grow. The once narrowly defined field of Blood Banking now encompasses involvement in major new Cellular Therapy/Regenerative Medicine research protocols related to treatment of patients with cancer as well as renal, hepatic and cardiac illnesses. This in turn provides opportunities for residents and fellows to consider robust careers in the field of Transfusion Medicine. In this manner we will move forward with one eye on the past and another on the promising future.