M. Mulargia

HLA antigen distribution in different clinical subgroups demonstrates genetic heterogeneity in lichen planus.

Summary HLA‐A, B, Cw, DR and DQ antigens were serologically determined in 105 patients suffering from lichen planus (LP). Of these patients, 87 had idiopathic LP and 18 had secondary LP. In the first group, 43 had cutaneous LP without mucosal lesions, 17 had cutaneous LP with mucosal lesions and 27 had purely mucosal LP. No HLA antigen was found to be significantly associated with secondary LP or with mucosal idiopathic LP. In cutaneous idiopathic LP with or without mucosal lesions, the HLA‐DR1 and DQ1 antigen frequency was significantly increased, and that of HLA‐DQ3 significantly decreased. Among the HLA‐DR1 cutaneous idiopathic LP patients, 78.5% carried the DRB1*0101 allele, and 214% the DRBI*0102 allele, compared with 35.7 and 67.8%, respectively, of the HLA‐DR1 controls. Our data demonstrate that idiopathic LP is influenced by HLA‐associated genetic susceptibility and resistance factors not involved in secondary LP, and that cutaneous idiopathic LP is a genetically and therefore pathogenetically different condition from purely mucosal idiopathic LP.

Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department – Cagliari University (Italy)

Background  Allopurinol is extensively prescribed for conditions associated with urate excess, despite being responsible for severe cutaneous adverse drug reactions (ADR).

Adult celiac disease is frequently associated with sacroiliitis

No data are available on the presence and frequency of peripheral or central joint disease, routinely determined by bone scintigraphy with 740 MBq of [99mTc]MDP, in adult celiac disease. Bone scintigraphy was carried out to detect early acute inflammatory lesions in 22 adult celiac patients (15 females and seven males; mean age 36.72 years, range 17–63). Bone scintigraphy was positive for sacroiliitis in 14 cases (63.6%). Except in the case of one patient suffering from rheumatoid arthritis, laboratory data were normal. Our data suggest that as in other chronic intestinal diseases, celiac disease in adults, is frequently associated with central joint disease. This high incidence of sacroiliitis, the joint disease most frequently found in our patients, has not been previously reported in other series. We believe, therefore, this difference could be explained by the different methodology used for the screening of joint difference could be explained by the different methodology used for the screening of joint disease.

The role of killer immunoglobulin-like receptor haplotypes on the outcome of unrelated donor haematopoietic SCT for thalassaemia

Recent insight into the pathophysiology of acute GVHD after allogeneic haematopoietic SCT has led to a growing interest in the role of natural killer (NK) cells. NK cell cytotoxicity is mainly regulated by the interaction of activating and inhibitory killer immunoglobulin-like receptors (KIRs) with their respective ligands. To investigate the impact of KIRs and their ligands on haematopoietic SCT outcome, we performed a retrospective study of 78 transfusion-dependent thalassaemia patients (median age 10 years, range 1–29 years) transplanted from an unrelated donor selected using high-resolution molecular typing for both class I and II loci after a myeloablative conditioning regimen. GVHD prophylaxis consisted of CsA, short-term MTX and anti-thymocyte globulin in all patients. We found that patients transplanted from donors homozygous for KIR haplotype A had a greater risk of developing grade II–IV acute GVHD compared with those transplanted from a donor carrying at least one B haplotype (hazard ratio=4.5, 99% confidence interval=1.2–17.1, P=0.003). Our study suggests that KIR genotyping of donor and recipient pairs could contribute to the identification of patients at high risk for developing severe complications of haematopoietic SCT and thus may help with the choice of intensity of GVHD prophylaxis.

THE HLA-DRB1*0101 ALLELE IS RESPONSIBLE FOR HLA SUSCEPTIBILITY TO LICHEN RUBER PLANUS

Serological studies have demonstrated that lichen ruber planus is associated with the HLA‐DR1 antigen. This association was also confirmed by us in the Sardinian population. To establish which DRB1 molecular alleles are involved, we studied a selected group of 14 DR1 positive patients affected by cutaneous idiopathic lichen planus and a group of DR1 positive healthy controls using PCR with sequence‐specific primers (PCR‐SSP).

Classic Kaposi's sarcoma in Sardinia: HLA positive and negative associations

Background  The incidence of classic Kaposis sarcoma (CKS) in northern Sardinia is one of the highest in the world.

Association of the HLA-A2, Cw2, B27, S31, DR2 haplotype with Ankylosing Spondylitis. A possible role of non-B27 factors in the disease

With the aim of searching for HLA haplotypes and non-B27 allele frequency variations in Sardinian AS patients, HLA-A, B, Cw, DR, DQ and Bf, C4A and C4B typing and haplotype assignment was carried out in the families of 25 AS patients and in 44 healthy individuals, all B27 heterozygotes. In the AS patients a significant increase of the A2, Cw2, B27, DR2, DQ1 haplotype was found. This depends only partially on the linkage disequilibrium existing in the Sardinian population between B27 and the other alleles of this haplotype, and rather seems to be due to a primary association of Cw2 and DR2 alleles with AS. Preliminary data seem to show that this haplotype bears the S31 complotype and the DRB1*1601 allele both in the AS patients and in the healthy controls. The pathogenetic implications of these findings are discussed.

Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm.

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin‐like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft‐versus‐host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7–10·1, P = 0·002] and transplantation‐related mortality (HR 4·7, 95% CI 1·6–14·2, P = 0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA‐C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9–19·2, P = 0·002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA‐KIR ligand group and the donor carried two or more activating KIRs (HR 6·8, 95% CI 1·9–24·4, P = 0·005). By interpolating the number of donor activating KIRs with recipient HLA‐C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision‐making.

Absence of activating killer immunoglobulin-like receptor genes combined with hepatitis C viral genotype is predictive of hepatocellular carcinoma

Killer immunoglobulin-like receptors and their human leukocyte antigen class I ligands have a critical role in natural killer cell response to viral pathogens and tumors. To investigate whether killer immunoglobulin-like receptor genes could influence the chronic course of hepatitis C virus infection and/or progression to hepatocellular carcinoma we retrospectively analyzed a cohort of 228 patients transplanted for hepatitis C virus-induced cirrhotic end stage liver disease, combined or not with hepatocellular carcinoma. We found that patients completely lacking activating killer immunoglobulin-like receptor genes had a high risk of developing hepatocellular carcinoma. Hepatitis C viral genotype and viral load are other risk factors that can influence the course of chronic hepatitis C virus infection. In our study, the risk conferred by hepatitis C viral genotypes was enhanced in patients lacking activating killer immunoglobulin-like receptors. These results point to an important role for activating killer immunoglobulin-like receptors in the control of hepatitis C virus infection and progression to hepatocellular carcinoma. In clinical practice, assessment of killer immunoglobulin-like receptor and hepatitis C viral genotype combinations should allow for more accurate monitoring of patients with chronic hepatitis C virus infection.

Familial autoimmune MuSK positive myasthenia gravis

The familial occurrence of autoimmune myasthenia gravis (MG) with anti-acetylcholine receptor antibodies (AChR Ab) has been rarely reported. Different antibody specificity in family members has also been described. To our knowledge, a familial form of MuSK Ab positive MG has never been reported. We studied the HLA allele profile in a family with two sisters affected by MuSK positive MG.