A novel FOXF1 mutation associated with alveolar capillary dysplasia and coexisting colobomas and hemihyperplasia.

Alveolar capillary dysplasia (ACD) is a rare and lethal cause of hypoxic respiratory failure in the neonate. Here we describe a term neonate with ACD that was found with a previously unreported p.Arg86Pro mutation in the FOXF1 (Forkhead Box-F1) gene and coexisting congenital anomalies, including colobomas of the iris and hemihyperplasia. This unique clinical presentation may indicate a novel, yet unconfirmed disease association for mutations in the FOXF1 gene. Rapid mutation analysis in FOXF1 may provide noninvasive early confirmation of ACD in neonates with respiratory failure and can aid in clinical decision making.

Large granular lymphocyte expansions in Felty's syndrome have an unusual phenotype of activated CD45RA+ cells.

One-third of patients with Felty's syndrome (FS) have significant clonal expansions of CD3+ CD8+ large granular lymphocytes (LGLs) in their peripheral blood. The reasons for this are unclear, but one hypothesis is that they are activated antigen-specific cells of pathogenic relevance. Cytofluorographic analysis of activation markers demonstrated that the cell surface phenotype of these expansions was CD57+, HLA-DR+, IL-2R-, Leu-8+, CD69+, LFA-1+, ICAM-1+, VLA-4+, i.e. 'activated' T cells. However, they also expressed the phenotype CD45RA+, CD45RBbright, CD45RO-, usually associated with 'naive' cells. This could result from aberrant activation, malignant transformation or from a 'reversal' of CD45 phenotype following chronic antigenic stimulation. In three patients with RA and non-clonal LGL expansions, a more variable phenotype was found. In one of these patients, the expanded population was identified in the peripheral blood, but not the synovial fluid. This may suggest that, at least in this individual, any pathogenic effect is exerted systemically.

Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies.

Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.