Alessandro Granito

Usefulness of antibodies to deamidated gliadin peptides in celiac disease diagnosis and follow-up.

The prevalence of the recently described deamidated gliadin peptide antibodies was compared with that of the routinely used antigliadin, antiendomysial, and tissue transglutaminase antibodies in the sera of 128 untreated celiac patients and 134 controls. Sensitivity and specificity for celiac disease were 83.6 and 90.3% for IgA and 84.4 and 98.5% for IgG antibodies to deamidated gliadin peptides. The new test displayed higher diagnostic accuracy than antigliadin antibodies and, although less sensitive than antiendomysial and tissue transglutaminase antibodies, showed significantly higher specificity than tissue transglutaminase antibodies (Pxa0<xa00.001). Persistence of peptide antibodies after gluten withdrawal was an expression of low compliance with the diet and of the lack of improvement of the intestinal mucosa. The combined use of tissue transglutaminase and deamidated gliadin peptide antibodies seems to be a very useful tool for celiac disease diagnosis. Moreover, antibodies to deamidated gliadin peptides can be helpful in disease follow-up.

Antibodies to SS-A⁄Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis

Background Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders.

Clinical Findings and Anti-Neuronal Antibodies in Coeliac Disease with Neurological Disorders

Background: Little is known about the clinical and immunological features of coeliac disease patients with neurological disorders. In a large series of adult coeliac disease patients, we investigated the prevalence of neurological disorders and anti-neuronal antibodies, along with the clinical course. Methods: Neurological symptoms were investigated in 160 consecutive patients (120 F, 40 M) with biopsy-proven coeliac disease. Anti-neuronal antibodies to central/enteric nervous systems were investigated in all neurological patients, 20 unaffected ones and 20 controls. Results: Thirteen (8%) patients had neurological disorders, including epilepsy ( n = 3), attention/memory impairment ( n = 3), cerebellar ataxia ( n = 2), peripheral neuropathy ( n = 2), multiple sclerosis ( n = 1), Moyamoya disease ( n = 1) and Steinerts disease ( n = 1). No significant demographic or clinical differences (gastrointestinal or other gluten-related signs) were found between patients with and without neurological involvement. In all but 2 of the 13 cases, the neurological disorder preceded diagnosis of coeliac disease. Neurological symptoms improved or disappeared in 7 patients who started a gluten-free diet within 6 months after neurological onset, and in none of 4 patients who began later. Prevalence of central nervous system antineuronal antibodies was significantly higher in neurological (61%) than in other patients (5%) ( P = 0.0007) or controls (0%) ( P = 0.00001). Conclusions: Coeliac disease can sometimes present in the guise of a neurological disorder, which may greatly improve when a gluten-free diet is started promptly. Therefore, the possible presence of coeliac disease needs to be carefully considered in patients with cerebellar ataxia, epilepsy, attention/memory impairment or peripheral neuropathy.

Hepatitis C and autoreactivity

After the discovery of HCV in 1989 a great amount of data has been produced in order to identify a possible aetiology for a number of idiopathic diseases, especially those with a suspected immune origin. Many associations have not been confirmed by prospective studies (as in the case of autoimmune hepatitis); other immune abnormalities, such as the emergence of non organ-specific autoantibodies and cryoglobulins, have been reported by many specific studies. To date, the link between HCV and autoreactivity is tentatively explained on the basis of sequence homologies shared by the HCV polyprotein and self proteins (such as CYP 2D6, target of anti-LKM1) (molecular mimicry mechanism); a second interpretation relies on the demonstration that the HCV - B lymphocyte interaction is able to induce a polyclonal B cell activation, an important cofactor for the development of clinically relevant B-lymphocyte autoimmune disorders. In this review we will focus on the major aspects of the autoimmune phenomena in HCV-infected patients, their clinical and therapeutical implications.

Evidence of a Genetic Basis for the Different Geographic Occurrences of Liver/Kidney Microsomal Antibody Type 1 in Hepatitis C

Antibodies to liver/kidney microsome type 1 occur in Italian patients with hepatitis C, but rarely develop in North American patients. Our goals were to compare the frequencies of the HLA markers associated with autoimmune expression in Italian and North American patients with chronic hepatitis C and to determine genetic bases for regional differences in antibody production. HLA B8, DR3, DR4, DR7, DR11, DR13, DQ2, and the B8-DR3-DQ2 haplotype were determined by microlymphocytotoxicity and polymerase chain reaction in 105 Italian patients (50 with microsomal antibodies), 100 North American patients (none with microsomal antibodies), and Italian and North American healthy control subjects. Italian patients with microsomal antibodies differed from North American patients without these antibodies by having a higher frequency of HLA DR7 (54% vs. 27%, P=0.002). HLA DR7 occurred more frequently in seropositive Italian patients than in seronegative counterparts (54% vs. 11% P < 0.0001), Italian healthy control subjects (54% vs. 29%, P=0.0009), and North American healthy control subjects (54% vs. 19%, P < 0.0001). The frequency of HLA DR7 was similar in North American patients and controls (27% vs. 19%, P=0.2), but it was lower than in Italian controls (19% vs. 29%, P=0.059). Seropositive Italian patients had a lower frequency of HLA DR11 than seronegative Italian patients and Italian controls (18% vs. 34%, P=0.07, and 18% vs. 35%, P=0.02, respectively). In contrast to seropositive Italian patients, North American patients had HLA DR4 (30% vs. 12%, P=0.02), HLA DR13 (29% vs. 10%, P=0.01), and the B8-DR3-DQ2 haplotype (23% vs. 6%, P=0.01) more often. Similarly, HLA DR4 and the B8-DR3-DQ2 phenotype were more frequent in North American patients than in Italian controls (30% vs. 16%, P=0.005, and 23% vs. 7%, P=0.00002, respectively). HLA DR7 is associated with the development of microsomal antibodies in Italian patients with chronic hepatitis C. The lower frequency of HLA DR7 in North America could contribute to the rarity of these antibodies in this region. HLA DR11 may be protective against the development of microsomal antibodies in Italian patients, whereas HLA DR4, HLA DR13, and the B8-DR3-DQ2 haplotype may be protective in North American patients.

Systemic lupus erythematosus.

n engl j med 358;22 www.nejm.org may 29, 2008 2412 traditional Medicare program in the United States takes the opposite approach to cost sharing for these two tests. Although PSA testing has not been conclusively demonstrated to improve health outcomes and is thus not recommended for universal screening,1 PSA testing is free for Medicare beneficiaries with Part B coverage.2 In contrast, screening mammography reduces mortality from breast cancer and is strongly recommended in national guidelines,3,4 but traditional Medicare beneficiaries with Part B coverage must pay 20% of the cost of screening mammograms.2 Our findings from Medicare health plans, therefore, also have implications for cost sharing in the traditional Medicare program. Golden correctly notes that our study did not include estimates of changes in health spending associated with imposing a copayment for screening mammography. Previous research has found screening mammography for women over the age of 65 years to be highly cost-effective, with a cost per life-year saved similar to that of singledrug therapy for mild-to-moderate hypertension — approximately

Anti-ganglioside antibodies in coeliac disease with neurological disorders

34,000 to

Sera of Patients With Celiac Disease and Neurologic Disorders Evoke a Mitochondrial-Dependent Apoptosis In Vitro

88,000.5 By detecting breast cancers at an earlier stage, mammography may also avert treatment costs and morbidity associated with later-stage disease. Combined with our finding that modest copayments of

Anti-saccharomyces cerevisiae antibodies (ASCA) in coeliac disease

12 to

Clinical and serological profile of primary biliary cirrhosis in men

35 reduced biennial screening rates among elderly women by 8 percentage points, these factors provide a compelling rationale to eliminate cost sharing for screening mammography in the Medicare program.