Cornulin, a marker of late epidermal differentiation, is down-regulated in eczema.

BACKGROUND: Eczema is a common chronic inflammatory skin disorder which shows strong genetic predisposition. To identify new potential molecular determinants of the disease pathogenesis, we performed a gene expression study in an eczema mouse model. This analysis identified a marked down regulation of the cornulin gene (CRNN), a member of the epidermal differentiation complex, in the eczema-like skin. We then investigated CRNN as an eczema candidate gene and studied its polymorphism and the expression in the skin of eczema patients. METHODS: An eczema-like phenotype was induced in mice by allergen (Der p2) patching. Gene expression analysis was performed with the subtractive suppression hybridization method and validated by real time PCR and the transmission disequilibrium test was used to test for genetic associations in 406 multiplex eczema families. RESULTS: Der p 2 patched mice developed a localized eczema and a Th 2 skewed systemic response. Real time PCR analysis confirmed a down regulation of CRNN mRNA in eczema-like skin in the mouse model and in human eczema. The CRNN polymorphism rs941934 was significantly associated with atopic eczema in the genetic analysis (P = 0.006), though only as part of an extended haplotype including a known associated variant (2282del4) in the filaggrin gene. CONCLUSIONS: CRNN mRNA expression is decreased in eczematous skin. Further studies are needed to verify whether the associated cornulin polymorphism contribute to the genetic susceptibility in eczema.

Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis.

In a systematic analysis of global gene-expression patterns, we found that SOCS3 messenger RNA was significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls, and immunohistochemical analysis confirmed a similar elevation of SOCS3 protein. Furthermore, we found a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene in two independent groups of patients (P<.02 and P<.03). These results strongly suggest that SOCS3, located in a chromosomal region previously linked to the disease (17q25), is a susceptibility gene for atopic dermatitis.

Antibody binding to platelet antigens in acute and chronic idiopathic thrombocytopenic purpura: a platelet membrane ELISA for the detection of antiplatelet antibodies in serum.

A solid-phase platelet membrane enzyme linked immunosorbent assay (ELISA) was developed for the detection of circulating platelet binding IgG in serum. 18 out of 28 (64%) sera from patients with chronic idiopathic thrombocytopenic purpura (ITP) and 10 out of 21 (48%) sera from patients with acute ITP contained more platelet binding IgG than the mean +2 s.d. of 25 normal control sera. IgG-F(ab')2 fragments from two anti-PlA1 sera, from six out of seven positive chronic ITP sera and from four out of eight positive acute ITP sera bound to normal platelet membrane. When IgG-F(ab')2 preparations, which reacted with normal membrane, were tested against glycoprotein IIb-IIIa-deficient platelet membrane obtained from a patient with Glanzmann's thrombasthaenia, the reactions of F(ab')2 fragments from two anti-PlA1 sera, from three out of four acute ITP sera and from four out of six chronic ITP sera were reduced to control levels. It is concluded that IgG-F(ab')2 antibody binding to platelet specific antigens, some of which are associated with the glycoprotein IIb-IIIa complex, can be demonstrated not only in anti-PlA1 sera or sera from chronic ITP patients but also in sera from some patients with acute ITP. Moreover, when the IgG binding to platelet membrane of whole sera is tested, positive results may sometimes be ascribed to the presence of immune complexes.

Increased in vitro B-cell IgG secretion during acute graft-versus-host disease and infection. Observations in 50 human marrow transplant recipients.

B-cell antibody secretion by lymphocytes from 50 bone marrow transplant recipients and 42 healthy controls was studied in vitro using an indirect hemolysis-in-gel assay to determine Ig-class-specific plaque-forming cells (PFC). The numbers of PFC were determined in medium alone and after stimulation of lymphocytes with killed Staphylococcus aureus bacteria. The PFC responses for IgG, IgA, and IgM after stimulation with S. aureus were significantly lower in patients studied during the first 101 days after grafting compared to normals. Statistically significant increased IgG-PFC were found in patients who had acute graft-vesus-host disease (GVHD), grafts from HLA-nonidentical donors, or infections. Healthy patients studied more than 1 yr following transplantation had normal B-cell responses, but patients with chronic GVHD had deficient IgM production. The data suggest that antibody secretion by B cells varies in different marrow transplant patient subgroups and present a basis for further investigation of the interaction between lymphocyte subpopulations leading to antibody production.