Genetic susceptibility to keloid disease and transforming growth factor beta 2 polymorphisms.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown aetiopathogenesis. There is a familial predisposition to keloid scarring. The genes involved in the pathogenesis of abnormal dermal scarring have yet to be identified. Transforming growth factor beta (TGF beta) is a family of multifunctional cytokines, which play a central role in wound healing and fibrosis. The TGF beta 2 isoform is a member of this cytokine family and has previously been implicated in KD pathogenesis. We tested for an association between KD and two novel polymorphisms within the TGF beta 2 gene: an insertion polymorphism within the 59-untranslated region, 109 base pairs away from the initiation codon, and a single nucleotide polymorphism in exon one. We examined DNA samples from 101 patients with KD and 187 ethnically matched controls. No statistically significant differences in TGF beta 2 genotype or allele frequency distribution were observed between the patients and the controls. We believe this to be the first report of a case-control association study in KD and TGF beta 2 polymorphisms.     

Anti-Sc1 in pregnancy

Anti-Sc1 was detected in a gravida-2 patient at 12 weeks' gestation. At 29 weeks, the antibody was found to be of the IgG3 subclass with a titer of 16, score 36, by the indirect antiglobulin test, and it produced 7 percent lysis by antibody-dependent cellular cytotoxicity (ADCC) assay, a finding that suggested an unaffected fetus. The titer remained constant throughout the pregnancy, as did the IgG subclass and activity in the ADCC assay. At delivery of the full-term infant, the cord hemoglobin was 13.5 g per dL and the direct antiglobulin test was positive (3+) with anti-IgG. The infant did not require transfusion. A sample taken 9 weeks after delivery showed 44 percent lysis in the ADCC assay. The anti-Sc1 titer was 32, score 65.     

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia

Background  Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.
Aim  To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus.
Methods  We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients.
Results  Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1–positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions.
Conclusion  These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

Conflicts of interest

None declared.     

Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition

As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.     

Evidence that Wra and Wrb are antithetical

Studies on 24 Wr(a+b+) and 23 Wr(a-b+) blood samples, using anti-Wrb in the enzyme-linked antiglobulin test (ELAT), have shown that Wr(a+b+) red cells bind, on average, a little over half the amount of anti-Wrb bound by Wr(a-b+) red cells. Similarly, ELAT studies using six different anti-Wra and 10 Wr(a+b+) samples, as well as red cells from the original Wr(a+b-) proposita, have shown that Wr(a+b+) red cells bind about half the amount of anti-Wra bound by Wr(a+b-) red cells. Various pitfalls that can arise when the ELAT is used to measure antigen ratios on red cells have been avoided but are described. This conclusive evidence that Wra and Wrb have an antithetical relationship is discussed in light of the knowledge that a ficin-resistant portion of MN sialoglycoprotein (SGP), when carried in liposomes, can inhibit anti-Wrb. It is possible that Wra, Wrb, or both may encode a post-translational change in MN SGP, or production of transferases that glycosylate membrane lipids that affect in situ orientation of MN SGP, or production of protein band 3 that then forms a complex with MN SGP at the red cell membrane surface.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

JMH variants: serologic, clinical, and biochemical analyses in two cases

BACKGROUND: JMH is a high-frequency red cell blood group antigen that resides on a 76- to 80-kDa glycosylphosphatidylinositol-linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH-variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH-variant antigen and produced alloanti-JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies and human antibodies to JMH were used in hemagglutination, radioimmunoassay, and Western blot testing of red cells from two JMH- variant patients; antiserum from one of these patients was also used in biochemical studies. In addition, in vivo survival of JMH-positive red cells was studied in the same patient. RESULTS: Biochemically, both examples of red cells with the JMH-variant phenotype expressed a JMH protein with a molecular weight similar to that of the normal JMH protein. For both patients, family studies suggested an autosomal recessive pattern of inheritance. Survival study demonstrated reduced in vivo red cell survival in one patient. CONCLUSION: JMH-variant phenotypes express a protein of normal molecular weight and are inherited in an autosomal recessive pattern. Furthermore, individuals with this phenotype can produce clinically significant antibodies.     

Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation in an infantwith schaaf-yang syndrome - Expanding the phenotypic spectrum

We report a novel patient with the phenotypic characteristics of Schaaf-Yang syndrome. In addition, the patient has a severe chronic digestive malfunction, rendering him dependent on intermittent enteral supplementation. To our knowledge, this is the first report of Schaaf-Yang syndrome associated with severe chronic digestive malfunction manifesting with both a malrotation and signs of a chronic intestinal pseudo-obstruction.