ABSTRACT
BACKGROUND: Allopurinol is extensively prescribed for conditions associated with urate excess, despite being responsible for severe cutaneous adverse drug reactions (ADR). OBJECTIVE: A cross-sectional survey of allopurinol cases observed at the main Dermatology Department with inpatients facilities in southern Sardinia. (approx 560,836 inhabitants). MATERIAL AND METHODS: Data collection of all consecutive patients referred for ADR between 2001 and 2010. Causality assessment followed the WHO Collaborating Centre for Drug Monitoring criteria; illness severity score was adopted for toxic epidermal necrolysis (SCORTEN). RESULTS: Allopurinol was the culprit drug in 84 of 780 cutaneous ADR cases (10.7%; 8.4 cases/year). Mean age was 74 years, 58% of the patients were female, 95% of patients required hospitalization. Clinical forms were maculo-papular eruptions (34 cases), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (31 cases), vasculitis (six cases), Drug Rash Eosinophilia and Systemic Symptoms (DRESS) (three cases), Acute Generalized Exanthematous Pustolosis (AGEP) (three cases), Pityriasis rosea-like eruption (three cases), lichenoid dermatitis (two cases), fixed drug eruption (one case), erythroderma (one case). The indication for allopurinol prescription was asymptomatic hyper-uricemia in 95% of the patients. Twelve patients were under allopurinol dosage adjustment according to creatinine clearance. Final causality assessment was definite for 12% of the cases and probable for the remaining 88%. Full recovery was achieved in 88% of subjects; ten SJS/TEN patients died (12% overall mortality; 32% mortality of the SJS/TEN cases). CONCLUSION: Considering the populations size of Southern Sardinia, is plausible that 1.5/100,000 Sardinian will be affected by allopurinol related ADR per year. Advanced age, and inappropriate allopurinol prescription were the main conditions affecting morbidity and mortality.
Subject(s)
Allopurinol/adverse effects , Skin/drug effects , Allopurinol/therapeutic use , Cross-Sectional Studies , Data Collection , Hospital Departments , Hospitals, University , Humans , ItalyABSTRACT
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.
Subject(s)
Hematopoietic Stem Cell Transplantation , Receptors, KIR/immunology , Thalassemia/surgery , Adolescent , Adult , Child , Child, Preschool , Female , Gene Frequency , Genotype , Graft vs Host Disease/immunology , Haplotypes , Humans , Infant , Killer Cells, Natural/immunology , Male , Receptors, KIR/genetics , Retrospective Studies , Thalassemia/immunology , Tissue Donors , Treatment Outcome , Young AdultABSTRACT
We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.
Subject(s)
HLA-C Antigens/genetics , Psoriasis/genetics , Psoriasis/immunology , Adolescent , Adult , Aged , Alleles , Case-Control Studies , Child , Child, Preschool , Chromosome Mapping , Female , Genes, MHC Class I , Haplotypes , Histocompatibility Antigens Class I , Humans , Infant , Male , Microsatellite Repeats , Middle Aged , Proteins/geneticsABSTRACT
A psoriasis susceptibility locus has been mapped to the HLA region in the proximity of the HLA-C locus. This critical region also contains the CDSN gene coding for the corneodesmosin protein. In a case-control association study of psoriasis in the Sardinian population, we analyzed the allele distribution of eight intragenic SNPs (positions 619, 767, 1215, 1118, 1236, 1243, 1331, 1593) of the CDSN gene and the six haplotypes that are coded by these SNPs. Our study showed that these CDSN haplotypes are very stable and well-conserved in the Sardinian population. The CDSN2 haplotype was found to be associated with susceptibility to psoriasis. The association did not depend upon any one of the intragenic SNPs taken separately. At the HLA-C locus, the Cw6 and Cw7 alleles were dragged along by linkage disequilibrium with the CDSN2 haplotype and only revealed a trend towards association with the disease. Therefore, the intragenic SNPs of the CDSN gene and the HLA-Cw6 and Cw7 alleles are not directly involved in susceptibility to psoriasis. However, the strong association of the CDSN2 haplotype suggests a possible role for the CDSN gene and its chromosome region in susceptibility to psoriasis.
Subject(s)
Genetic Predisposition to Disease , Glycoproteins/genetics , Polymorphism, Single Nucleotide , Psoriasis/genetics , Female , HLA-C Antigens/genetics , Haplotypes , Humans , Intercellular Signaling Peptides and Proteins , Italy , Male , Psoriasis/pathologyABSTRACT
BACKGROUND AND OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a widely accepted therapeutic approach in homozygous beta-thalassemia. However, the majority of patients do not have a genotypically identical donor within the family. This prompted us to conduct a pilot study to investigate the feasibility of matched unrelated bone marrow transplantation in thalassemia. The major drawback was the high risk of immunologic and transplant-related complications, mainly graft-versus-host disease (GvHD) and graft failure. DESIGN AND METHODS: Our aim was to reduce this risk through careful selection of donor/recipient pairs. HLA haplotypes that show a high linkage disequilibrium among their class I, class II and class III alleles are considered extended or ancestral haplotypes. RESULTS: These haplotypes are conserved and can be shared by apparently unrelated individuals. Our study shows that matching for these haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. In fact, results were comparable to those obtained in transplants using HLA-identifical family donors. INTERPRETATION AND CONCLUSIONS: Better results were obtained in patients with lesser iron overload and when the donor shared an identity for the DPB1 alleles.
Subject(s)
Bone Marrow Transplantation/statistics & numerical data , Transplantation, Homologous/statistics & numerical data , beta-Thalassemia/therapy , Adolescent , Adult , Bone Marrow Transplantation/immunology , Child , Child, Preschool , Female , Histocompatibility Testing , Humans , Italy , Male , Retrospective Studies , Risk Assessment , Treatment Outcome , beta-Thalassemia/immunologyABSTRACT
The hypothesis of a possible selective role of malaria in HLA allele frequency variations was investigated in Sardinia by typing completely 1,039 individuals for HLA: 536 from six lowland villages exposed to malaria until 1948, and 503 from six highland villages with no history of malaria. Another 1,928 individuals from 136 villages scattered all over the island were studied to establish if the HLA allele frequencies among villages correlated with the malaria incidence and/or altitude above sea level. Only the HLA-B35 allele yielded significantly higher frequencies in the lowland versus the highland villages (P<1 x 10(-5)). The observed B35 variance was 9.5 times higher than expected in the absence of selection, showing an adaptive origin. The highly significant positive correlation found between HLA-B35 frequency and malaria in 136 villages suggests that malaria has been the selective factor for HLA-B35 in Sardinia.
Subject(s)
Genetic Variation , HLA-B35 Antigen/genetics , Malaria, Falciparum/immunology , Alleles , Altitude , Gene Frequency , Globins/genetics , HLA-B Antigens/genetics , Humans , Italy , Mathematical Computing , Microsatellite Repeats , Mutation , beta-Thalassemia/genetics , beta-Thalassemia/immunologyABSTRACT
HLA class II antigens and DRB1, DQA1, DQB1 alleles were studied in 16 Italian and in 16 Sardinian patients with pemphigus vulgaris (PV). In the last group the complete HLA A-DQ haplotypes, including the complotypes, were defined by family studies. As in other populations, two PV susceptibility haplotypes were found: HLA-DRB1*0402, DQA1*0301, DQB1*0302 and HLA-DRB1*1401, DQA1*0104, DQB1*0503. The first haplotype was largely prevalent in the Sardinian patients and was a part of the extended haplotype HLA-A2, Cw4, B35, S31, DR4, DQ8. The strength of the allele associations to PV is in agreement with the view that the main PV susceptibility genes are the DRB1*0402 and DQB1*0503 alleles. A genetic resistance to PV seems to be conferred by the HLA-DR3, DQ2 haplotype in the Sardinian population.
Subject(s)
Alleles , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Pemphigus/immunology , Disease Susceptibility/immunology , Gene Frequency , Genetic Predisposition to Disease , Genotype , HLA-A Antigens/blood , HLA-A Antigens/classification , HLA-B Antigens/blood , HLA-B Antigens/classification , HLA-C Antigens/blood , HLA-C Antigens/classification , HLA-DQ Antigens/blood , HLA-DQ Antigens/classification , HLA-DR Antigens/blood , HLA-DR Antigens/classification , Haplotypes , Histocompatibility Antigens Class II/blood , Histocompatibility Antigens Class II/classification , Histocompatibility Antigens Class II/genetics , Humans , Italy , Pemphigus/bloodABSTRACT
We report 4 new families with Kaposi's sarcoma, occurring in 2 members of the same family (2 pairs of brothers, uncle and nephew and father and son) in a series of 160 patients with Kaposi's sarcoma. In addition, HLA typing was also carried out for 6 of the 8 patients. A detailed review of the literature is also presented. The total number of familial cases of Kaposi's sarcoma is low (only 30 cases are described); the great majority of these cases consist of siblings and Italians.
Subject(s)
Sarcoma, Kaposi/genetics , Skin Neoplasms/genetics , Aged , Aged, 80 and over , Fatal Outcome , HLA Antigens/analysis , Histocompatibility Testing , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Sarcoma, Kaposi/diagnosis , Sarcoma, Kaposi/epidemiology , Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiologyABSTRACT
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 disease.
Subject(s)
Arthritis/complications , Celiac Disease/complications , Sacroiliac Joint , Adult , Arthritis/diagnosis , Arthritis/diagnostic imaging , Arthritis/epidemiology , Celiac Disease/epidemiology , Female , Humans , Incidence , Male , Radionuclide Imaging , Technetium Tc 99m MedronateABSTRACT
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 21.4% the DRB1*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.
Subject(s)
HLA-A Antigens/analysis , HLA-DR Antigens/analysis , Lichen Planus/immunology , Adult , Aged , Disease Susceptibility , Female , Genetic Heterogeneity , Histocompatibility Testing , Humans , Lichen Planus/genetics , Male , Middle AgedABSTRACT
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). Comparisons between the allele frequencies in patients and controls showed a positive association with cutaneous idiopathic lichen planus for the DRB1*0101 allele (RR = 5.8, P = 0.0097), DRB1*0101 and DRB1*0102 are associated with the same DQA1 and DQB1 alleles and are different only for two amino acids in positions 85 and 86 of the DRB1 gene. In our case report predisposition to cutaneous idiopathic lichen planus is correlated with a valine in position 85 and a glycine in position 86 at the second exon of the DRB1 gene.
Subject(s)
HLA-DR Antigens/genetics , Lichen Planus/genetics , Lichen Planus/immunology , Alleles , Amino Acid Sequence , Base Sequence , Case-Control Studies , DNA Primers/genetics , Female , HLA-DRB1 Chains , Humans , Male , Polymerase Chain Reaction , Polymorphism, GeneticABSTRACT
The HLA-B49 DR4 haplotype, which is rare in Caucasoid populations, has a frequency in Sardinia of approximately 6% and a very strong linkage disequilibrium (LD). To better understand its genetic structure, the Bf, C4A and C4B Class III alleles were studied in 56 healthy unrelated Sardinian subjects of B49 DR4 phenotype and in 24 of their families. Moreover, 14 sick subjects with the same phenotype were examined together with five of their families. A group of 285 haplotypes belonging to randomly selected individuals was used as a control population sampling. The distribution of the Bf, C4A and C4B alleles among the healthy probands revealed two main groups of association: one major group of 36 subjects (64.3%) with the BfF, C4A3 and C4B4 alleles and one minor group of 14 subjects (25%) with BfS, C4AQ0 and C4B1. A similar subdivision was also observed in the small group of patients. The family analysis confirmed these results and showed two different B49 DR4 extended haplotypes: one with the F34 complotype in 79.1% of the probands (delta x 1000 = 49.0) and the other with the S01 complotype in 20.8% of the probands (delta x 1000 = 17.3). The first one, in LD with the A1 and Cw7 alleles, has not yet been reported in other populations. The second one seems to be identical to a haplotype already reported in the Spanish population. The molecular analysis of the DRB1 locus carried out in 20 of the 70 probands demonstrated that, in both haplotypes, DR4 was represented by the DRB1*0405 allele.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
HLA-B Antigens/genetics , HLA-DR4 Antigen/genetics , Haplotypes , White People/genetics , Alleles , DNA/genetics , Female , Humans , Italy , Linkage Disequilibrium , Male , Pedigree , PhenotypeABSTRACT
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.
Subject(s)
HLA Antigens/analysis , HLA Antigens/classification , Haplotypes , Spondylitis, Ankylosing/genetics , Spondylitis, Ankylosing/immunology , Adult , Female , Gene Frequency , HLA Antigens/physiology , Humans , Male , Middle AgedSubject(s)
Bone Marrow Transplantation , beta-Thalassemia/surgery , Adolescent , Adult , Bone Marrow Purging , Bone Marrow Transplantation/adverse effects , Busulfan , Child , Child, Preschool , Cyclophosphamide , Female , Graft Survival , Graft vs Host Disease/prevention & control , Histocompatibility Testing , Humans , Italy , Male , Treatment OutcomeABSTRACT
A study on the HLA structure of the Sardinian population was carried out on 551 healthy unrelated families representing all of the island districts. Altogether 2202 HLA-A, B, Cw, DR individual haplotypes and 853 different haplotypes were determined. Cavalli-Sforza and Edwards' genetic distance index for the total of 62 tested alleles showed a modest heterogeneity between one district and another (0.09-0.16). The genetic distance between Sardinians and the rest of the Italian population was 0.23 (0.22-0.26) and progressively increased in comparisons with caucasoids (0.26), negroids (0.34) and mongoloids (0.41). Sixty-three two-locus haplotypes with a high positive linkage disequilibrium were observed in our family sample. The percentages of two-locus haplotypes in LD shared with other populations turned out to be 45% with caucasoids, 20% with negroids and 10% with mongoloids. The distribution of the A, B, Cw, DR haplotypes is shown with 673 of them represented only once or twice, and 10 (1.2%) 14-322 times each. Of the latter, 8 are extended haplotypes, 6 of which characterize the Sardinian population. The analysis of our data suggests that the present-day Sardinian population is the result of a superposition of different populations, mainly consisting of caucasoids on a pre-caucasoid paleo-Mediterranean substratum.
Subject(s)
Ethnicity , HLA Antigens/genetics , Adult , Alleles , Child , Ethnicity/history , Female , Gene Frequency , Haplotypes , History, Ancient , Humans , Italy , Male , White People/geneticsABSTRACT
479 families, each with a proband affected by homozygous beta-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between beta-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.
Subject(s)
Gene Frequency/genetics , HLA Antigens/genetics , Thalassemia/genetics , Alleles , Female , Gene Frequency/immunology , Genetic Linkage/genetics , Genetic Linkage/immunology , Genotype , HLA Antigens/analysis , HLA-A Antigens/genetics , HLA-A Antigens/immunology , HLA-B Antigens/genetics , HLA-B Antigens/immunology , HLA-C Antigens/genetics , HLA-C Antigens/immunology , HLA-DQ Antigens/genetics , HLA-DQ Antigens/immunology , HLA-DR Antigens/genetics , HLA-DR Antigens/immunology , Haplotypes/genetics , Haplotypes/immunology , Homozygote , Humans , Male , Phenotype , Sex Ratio , Statistics as Topic , Thalassemia/immunologyABSTRACT
HLA Class I and Class II antigens were studied in 103 unrelated Sardinian patients with Graves' disease (GD), 71 of whom had ophthalmopathy, and in 220 healthy controls. Molecular typing of the DQB1 allelic variants was carried out on 34 GD patients and 35 healthy controls, selected for the HLA-DR2-DQw1 phenotype. The results of the serological typing showed a positive association with the DR2 and the DQw1 antigens and a negative association with DR3 and DQw2 antigens. These associations were stronger in the GD patients with ophthalmopathy. The DQB1 molecular analysis in patients with the HLA-DR2-DQw1 phenotype revealed the presence of the DQB1*0502 allele in 91.1 per cent of the patients and in 82.2 per cent of the controls. In the Sardinian population GD seems to present a different HLA association than that observed in other Caucasian populations (DR3-Dw24). The DR2 and DQw1 positive associations may be explained by the high frequency of the DQB1*0502 allelic variant (37.7 per cent) which is rare in the other Caucasian populations. The absence of an association between DR3 and GD in Sardinia can be attributed to the very low frequency of the HLA-B8-DR3 (Dw24) haplotype. In fact, in the Sardinian population, DR3 is associated with the allelic variant Dw25 carried by the HLA-B18-DR3 haplotype.
Subject(s)
Graves Disease/immunology , HLA Antigens , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Base Sequence , DNA/genetics , DNA Probes, HLA , Female , Gene Frequency , Genetic Markers , Graves Disease/genetics , HLA Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class II/genetics , Humans , Italy , Male , Middle Aged , Molecular Sequence DataABSTRACT
This study was carried out in Sardinia, an Italian region with a very high IDDM incidence. HLA class I and class II antigens were studied in 97 unrelated IDDM patients, 33 complete families with at least one affected member each, and 559 healthy controls. Molecular typing of the DQB1 alleles was carried out in 31 patients and 61 controls. The haplotypes were determined by family studies. The HLA-DR3, DQw2, and DR4 antigens were positively associated with IDDM. The DR3 antigen was nearly always associated to B18 and frequently carried by the extended haplotype A30 Cw5 B18 3F130 DR3 DQw2. The genotype analysis of the patients showed a strong increase of the DR3/DR4 heterozygotes with a relative risk higher than that of the DR3 and DR4 homozygotes. The DR2 antigen was negatively associated with IDDM in the central island districts but not in the southern districts. The DQB1 molecular analysis showed only three alleles in the patients: DQB1*0201 (75.8 per cent), DQB1*0302 (16.1 per cent), and DQB1*0502 (8.1 per cent). These alleles are non Asp 57, so it would seem that nearly if not all Sardinian IDDM patients are NA/NA homozygotes. The DQB1*0502 allele, extremely rare in other Caucasian populations, represents in Sardinia about 70 per cent of the HLA-DR2 haplotypes, contributing to the increase of the pool of IDDM susceptible genes. Moreover it is carried in 27 per cent of the DR2 positive individuals with the extended haplotype A2 Cw7 Bw58 3F31 DR2 DQw1.AZH.