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Avi Livneh

Publications and source records attributed to Avi Livneh.

16 recordsLinked to original sources
PubMed2003

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever.

OBJECTIVE: The clinical profile in familial Mediterranean fever (FMF), including its major manifestation, amyloidosis, is influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF. METHODS: We investigated a sample of 277 FMF patients (154 men and 123 women), including 62 patients with nephropathic amyloidosis, in whom both FMF alleles had been identified. A detailed chart review, interview, and physical examination were undertaken to determine the patients' demographic characteristics, medical history, clinical manifestations, and treatment. The disease severity score was calculated from the Tel-Hashomer key. Genotypes at the SAA1 locus (isoforms alpha, beta, and gamma) were determined in all patients. The SAA1 13C/T polymorphism of the SAA1 promotor was analyzed in a subset of cases. RESULTS: The male:female ratio (154:123, or 1.3) was higher among patients with amyloidosis (40:22, or 1.8) compared with patients without amyloidosis (114:101, or 1.1). Logistic regression analysis showed that homozygosity for the M694V allele (odds ratio [OR] 4.27, 95% confidence interval [95% CI] 2.01-9.07), the presence of the SAAalpha/alpha genotype (OR 2.99, 95% CI 1.47-6.09), the occurrence of arthritis attacks (OR 2.43, 95% CI 1.17-5.06), and male sex (OR 1.73, 95% CI 0.90-3.33) were significantly and independently associated with renal amyloidosis. Disease severity was mainly influenced by MEFV mutations and was not associated with genotypes at the SAA1 locus. The SAA1 13T allele was rare, being associated mainly with the SAA gamma isoform, and not related to renal amyloidosis. CONCLUSION: Overall, disease severity and the development of amyloidosis in FMF are differentially affected by genetic variations within and outside the MEFV gene.

Amyloidosis↗
PubMed2003

Expansion of gammadelta T-cells in Behçet's disease: role of disease activity and microbial flora in oral ulcers.

Gammadelta T-cells participate in the immune response to infections and in autoimmunity by recognizing bacteria-derived and autologous antigens. The goal of this study was to evaluate the involvement of gammadelta T-cells in Behçet's disease (BD). Gammadelta T-cells in the peripheral-blood mononuclear cells (PBMCs) of Israeli patients with definite BD (n = 23), normal controls (n = 16), and patients with familial Mediterrranean fever (FMF; n = 20) were evaluated by means of flow cytometry. The responses of patient and control gammadelta T-cells to medium conditioned by microorganisms cultured from an oral ulcer of a patient with active BD were compared. The proportions of CD3(+) and CD8(+) cells in the PBMCs were not significantly different between groups. In contrast, gammadelta-T-cells accounted for 7.01% +/- 4.42% of the PBMCs in BD compared with 3.56% +/- 3.45% in FMF (P < .005) and 3.7% +/- 3.15% in normal individuals (P < .009). Their numbers were significantly higher during active disease than in remission (9.45% +/- 5.08% versus 2.27% +/- 3.3%; P < .009). The number of T-cell-receptor gammadelta(+) and Vdelta2(+) cells of BD patients, but not of controls, increased after 96 hours of culture in medium containing supernatant of microorganisms cultured from an oral ulcer in a patient with BD relative to their proportions in control medium: 58.2% vs 13.9% (P < .05) and 28% vs 9% (P < .04), respectively, of the cultured T-cells (n = 4).gammadelta T-cells are expanded in BD PBMCs during active disease. An exaggerated proliferative response to products released by microorganisms present in oral ulcers may play a role in this phenomenon.

Adult↗
PubMed2003

Colchicine in tear fluid of treated patients with familial Mediterranean fever.

PURPOSE: The study aimed to determine whether detectable concentrations of colchicine are present in the tear fluid of treated patients with familial Mediterranean fever (FMF) and thus demonstrate a possible route by which colchicine reaches the corneal surface. METHODS: Tear fluid samples (50-100 microL) were collected from eight FMF patients on long-term colchicine treatment. Colchicine tear fluid concentrations were determined in all patients by radioimmunoassay using goat anticolchicine antibodies and [3H]colchicine (Dupont, Wilmington, DE). RESULTS: Detectable concentrations of colchicine, with no apparent effect on the ocular surface, were found in all tear fluid samples (median, 0.46 ng/mL; range, 0.24-1.05 ng/mL). CONCLUSIONS: This study provides evidence of the route by which colchicine, given systemically, reaches the corneal surface and thus gives credence to the possible inhibitory effect of this drug on corneal wound healing in the cases described in the literature.

Adult↗
PubMed2003

Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism.

In the 1359 published patients with multiorgan cholesterol crystal embolism (CCE), the digestive system seems to be the third most frequently affected system. Yet, this system received hitherto only little attention in the medical literature. Therefore, the aim of the present study was to clinically characterize the subset of patients with CCE involving the digestive system, based on our institutional experience and a review of the literature. Cases with CCE in a 7-yr period (1995-2001) were sought in the computerized records of our medical center. Of the CCE patients, those with digestive system involvement that could be related to CCE were included in this study. The clinical features of CCE were determined and compared with those found in published series. Fourteen cases with CCE were identified, giving an annual incidence of 0.8 per 10(5). Digestive system involvement was found in five (36%) of the 14 patients. All five patients had established atherosclerosis. Precipitating factors were vascular manipulations or anticoagulation treatment in four of these five patients. Two patterns of disease appeared: acute catastrophic multiorgan disorder with poor prognosis and chronic and more indolent GI disease. Abdominal pain, GI bleeding, fever, and diarrhea were the most common manifestations, resulting from bowel infarction, mucosal ulcerations, hepatocellular liver disorder, and/or pancreatitis. CCE is a systemic disorder with a frequent involvement of the digestive system and protean clinical manifestations. It should, therefore, be considered in any gastroenterological patient with atherosclerosis and recent vascular manipulations or systemic anticoagulation.

Aged↗
PubMed2003

Clinical and diagnostic value of genetic testing in 216 Israeli children with Familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disease with diverse clinical presentation. The FMF gene (MEFV) has recently been cloned and 30 point mutations causing the disease have been identified. We appraised the value of mutation analysis as a diagnostic test for FMF in symptomatic pediatric patients, and explored the possible correlations between MEFV genotypes and the diverse phenotypic expression of the disease. METHODS: Two hundred sixteen children who met the clinical criteria for FMF underwent molecular genetic studies to detect the 3 most common mutations in the Israeli FMF patient population (M694V, V726A, E148Q). The mutations found were related to clinical presentation and disease severity, using the Tel-Hashomer severity score. RESULTS: Of the 216 children who fulfilled the diagnostic criteria for FMF, 82 (38.0%) had 2 of the tested mutations, 73 (33.8%) had only one mutation, and 61 (28.2%) had none of the mutations studied. The M694V was the most frequent mutation, detected in 174 of 432 MEFV alleles (40.0%). The V726A mutation was found in 39 alleles (9.0%) and the E148Q mutation in 25 (5.8%). The severity score correlated with the number of mutations. Children with no mutations presented at an older age compared to children with one or 2 mutations. Children homozygous for the M694V mutation presented at a younger age, had a higher severity score, and more commonly had arthritis. CONCLUSION: Limited genetic molecular testing for MEFV mutations may explain some of the FMF clinical variability, but is diagnostically ineffective. The use of clinical criteria remains essential in establishing the diagnosis of FMF.

Adolescent↗
PubMed2003

Male sex coupled with articular manifestations cause a 4-fold increase in susceptibility to amyloidosis in patients with familial Mediterranean fever homozygous for the M694V-MEFV mutation.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever, serositis, and a predisposition to the development of amyloidosis. The wide clinical variability of the disease has been partly attributed to MEFV allelic heterogeneity and partly to the influence of additional genetic and/or environmental modifiers. Of these, male sex was found to influence disease penetrance and susceptibility to amyloidosis. We investigated the role of sex as an independent contributor to the phenotypic profile in FMF and further defined the factors affecting disease expression and severity. METHODS: A total of 124 patients with FMF who were all homozygous for the M694V mutation, including 47 patients with nephropathic amyloidosis, were identified. A detailed chart review and physical examination were undertaken to determine demographic characteristics, history, clinical manifestations, and treatment, and we calculated the disease severity score from the Tel-Hashomer key. RESULTS: A preponderance of male patients was documented (73:51; 1.4). The overall male:female ratio was significantly higher among patients with amyloidosis (32:15; 2.1) compared to patients without amyloidosis (41:36; 1.1). FMF severity scores, independently calculated for male and female patients, were equally high (9.5 +/- 3.0 and 9.7 +/- 2.8, respectively). The frequency of arthritic attacks, significantly higher in women than men (p = 0.015), remained notably higher in male FMF patients with amyloidosis compared to male FMF patients without amyloidosis (p = 0.002). Significant correlation between arthritis attacks and amyloidosis was found (R > 0.285, p < 0.001). CONCLUSION: Susceptibility to renal amyloidosis is influenced both by sex and the occurrence of joint attacks, acting as 2 MEFV independent factors (OR 2.37, 95% CI 1.06-5.26 and OR 3.27, 95% CI 1.23-8.68, respectively).

Adult↗
PubMed2003

Analysis of the three most common MEFV mutations in 412 patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells. OBJECTIVES: To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q. RESULTS: The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001). CONCLUSIONS: Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.

Amyloidosis↗
PubMed2002

Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.

In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli sisters. These young women responded to environmental temperatures of 18 degrees C-7 degrees C with profuse sweating on large segments on their back and chest. Both had additional abnormalities, including a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend their elbows, and kyphoscoliosis. We have observed this disorder in two Norwegian brothers. Genome-wide screening in the two families, followed by saturation marker studies and linkage analysis, identified a 1.4-Mb homozygous candidate region on chromosome 19p12. The maximum multipoint LOD score was 4.22. In both families, DNA sequencing of 25 genes within the candidate region identified potentially deleterious CRLF1 sequence variants that were not found in unaffected control individuals. Our findings confirm that the cold-induced sweating syndrome is an autosomal recessive disorder that is probably caused by impaired function of the CRLF1 gene, and they suggest important developmental functions for human CRLF1.

Adolescent↗
PubMed2002

Thoracic and lung involvement in familial Mediterranean fever (FMF).

Lung involvement in FMF is limited mainly to transient pleuritis during acute attacks. Amyloidosis of the lung is rare and is associated with symptomatic involvement of other organs while remaining subclinical in itself. Vasculitis of the lung in FMF is possible because of the strong association between FMF and a variety of vasculitides. With the exception of one case of isolated pulmonary vasculitis, vasculitis of the lung in FMF has not been described. The claim that FMF protects against asthma has not been established, but this inverse association, if present, may be traced to linkage disequilibrium in which MEFV modifies the effect of asthma and atopic-related genes, or to eosinophil function. Mesothelioma has been reported in at least four patients with FMF and is related to chronic or recurrent stimulation of the serous membrane. Three patients had peritoneal mesothelioma, while one developed mesothelioma of the lung. Finally, thromboembolism should be considered, particularly in patients with FMF amyloidosis who present with respiratory distress.

Familial Mediterranean Fever↗
PubMed2002

The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurring attacks of fever and serositis. Five sequence alterations (M694V, V726A, M680I, M694I and E148Q), in the MEFV gene, account for the majority of FMF chromosomes. The wide clinical variability of the disease has been related to MEFV allelic heterogeneity. M694V homozygotes have a severe form of the disease. Mutations E148Q and V726A have reduced penetrance. The clinical features, associated with the M680I and the complex V726A-E148Q allele, are not well defined. This study aims to further characterise the phenotypic profile associated with the major MEFV mutations. We investigated 220 FMF patients, in whom both FMF alleles have been identified, and found that different genotypes are characterised by a specific allelic related clinical profile and penetrance. Homozygotes for the M694V mutation and the complex V726A-E148Q allele are the most severely affected and often endure renal amyloidosis. Homozygotes for the M680I and V726A alleles and compound heterozygotes for either the M694V or the V726A-E148Q alleles in combination with either the E148Q, the V726A or the M680I alleles are significantly less severely affected. The morbididity associated with the complex V726A-E148Q allele by far outweighs that associated with the V726A allele, bearing evidence to the fact that the E148Q mutation is not a benign polymorphism. These findings increase our understanding of the role of allelic variability in disease expression.

Africa, Northern↗
PubMed2002

Crohn disease in patients with familial Mediterranean fever.

Crohn disease and familial Mediterranean fever (FMF) are inflammatory diseases characterized by abdominal pain and fever. The concurrence of the 2 diseases (FMF-CD) may pose a challenge to diagnosis and treatment. We undertook the present study to determine the prevalence of Crohn disease in FMF and to characterize FMF-CD patients clinically and genetically. Using a computerized search, the patients of our FMF clinic were screened for a concomitant diagnosis of Crohn disease. Patients and their medical records were thoroughly examined, and their DNA was genotyped for mutations in the MEFV gene. Control groups of ethnically and sex-matched patients suffering from each of the diseases alone, either Crohn disease or FMF, were used for comparison. We identified 7 patients with concomitant Crohn disease and FMF, which is more than the expected prevalence in the general population (p = 0.03). Crohn disease presented at a significantly later age in the FMF-CD group (40.6 +/- 10.0 yr versus 26.2 +/- 11.4 yr; p < 0.004). Disease severity and other characteristics of Crohn disease were comparable to the Crohn disease control group. Contrary to the FMF control group patients, FMF in FMF-CD patients was characterized by a higher attack frequency (p < 0.05) and increased prevalence of amyloidosis (p < 0.02). The overall severity score was similar in both groups. In conclusion, Crohn disease appears to be more prevalent in FMF and presents later than in patients without FMF. FMF in this group of patients shows a higher attack frequency and is more often complicated by amyloidosis.

Abdominal Pain↗