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.     

High-dose chemotherapy and unpurged autologous bone marrow transplantation for acute leukemia in second or subsequent remission

The authors administered high-dose chemotherapy with cyclophosphamide, BCNU (carmustine) and VP-16 (etoposide) plus autologous bone marrow transplantation (ABMT) to 22 adult patients with relapsed acute leukemia in second or subsequent remission. The marrow was not treated ex vivo. The long-term, disease-free survival rate was 14%. Comparison of results with other treatments can be difficult because of patient selection biases. The concept of inversion (achievement of a longer remission with salvage therapy than with prior treatments) is proposed to compare treatment results. Three patients remain in complete remission beyond 4 years, with inversions. More intensive cytoreductive regimens will be needed to improve results.     

A survey of current prescribing practices of anti-inflammatory and urate-lowering drugs in gouty arthritis in New South Wales and Queensland

We recently have conducted a cross-sectional survey to determine the prescribing practices of rheumatologists and a random sample of general practitioners in New South Wales and Queensland. While in general there was agreement as to the preferred management of gout, several important differences were noted between the two groups of doctors. In particular, general practitioners were more liberal than were rheumatologists in their use of allopurinol. However, they were less likely to cover the introduction of allopurinol with anti-inflammatory agents, to titrate the dose against the serum uric acid level or to adjust the dose according to the serum creatinine level. A small number of doctors continued to use urate-lowering drugs as a routine in the treatment of entirely asymptomatic hyperuricaemia. The data indicate a continuing need to disseminate information regarding the preferred management of hyperuricaemic states.     

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.     

Heterogeneity of anti-U demonstrable by the use of papain-treated red cells

When red cells (RBCs) are treated with papain, one form of the U antigen, which we have named UPS (U papain-sensitive), is almost completely removed or denatured. A second form, UPR (U papain-resistant), remains unaltered on the treated RBCs. Tests on 42 examples of anti-U showed that two contained only anti-UPS, 19 contained only -UPR, and 21 contained separable -UPS and -UPR. In those sera containing both antibodies, anti-UPR was always the stronger of the two. These findings suggest 1) that UPS is located on the Ss sialoglycoprotein (glycophorin B) at a position distal to a papain-sensitive site or that the cleavage point is within the portion of the SGP that comprises UPS, and 2) that UPR is located between the papain-sensitive site and the RBC membrane. The UPS determinant was not denatured by neuraminidase, L-cysteine, trypsin, ficin, or alpha-chymotrypsin, and it was only partially denatured by pronase. The finding that RBCs treated with para-chloromercuribenzoic acid or para-chloromercuriphenyl sulfonic acid did not react with anti-UPR but did continue to react with anti-UPS suggests that the in situ configuration of UPR, but not UPS, is dependent on the presence of one or more disulfide bonds. RBCs of the S-s-U+(weak) phenotype were shown to carry markedly reduced amounts of both UPS and UPR.