Inducible nitric oxide synthase polymorphism is associated with susceptibility to Henoch-Schönlein purpura in northwestern Spain.

OBJECTIVE: To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schönlein purpura (HSP), and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Fifty-eight patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n=251) were genotyped by PCR based techniques for a multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of the NOS2A gene. RESULTS: HSP patients exhibited a significantly increased frequency of the NOS2A short (8-11) CCTTTn alleles (OR 1.64, 95% CI 1.09-2.47, p=0.017) and genotypes (OR 3.59, 95% CI 1.79-7.20, p=0.0002) compared to controls, particularly when patients with nephritis were compared with controls. However, when the NOS2A TAAA repeat polymorphism was assessed, no differences were found. CONCLUSION: Significant differences in the NOS2A promoter polymorphism allele and genotype frequency between HSP patients and controls suggest a potential role for this gene in the susceptibility to HSP and in the development of nephritis.

Interleukin 1beta gene polymorphism association with severe renal manifestations and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of the interleukin (IL)-1beta gene (-511 C/T) in the incidence of Henoch-Schönlein purpura (HSP) and determine its possible implication in severe systemic complications of HSP, in particular severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1beta gene (-511 C/T) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Forty-nine Caucasian patients (38 of them younger than 21 years) who fulfilled classification criteria for HSP and 148 controls were examined. No allele or genotype differences between the whole group of HSP and controls were observed. However, all 5 patients who developed severe nephropathy during the course of disease carried the rare T allele compared with only 16 of the remaining 44 patients (pcorr = 0.01). A significant association between carriage of the -511(IL-1beta) T allele and renal sequelae (pc = 0.02; OR: 3.6, 95% CI: 1.3-10.0) was also found. CONCLUSION: In unselected patients with cutaneous vasculitis who fulfill classification criteria for HSP, carriage of IL-1beta (-511) T allele appears to influence severity of renal involvement.

Lack of association between endothelial nitric oxide synthase polymorphisms and Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility and clinical expression of patients with cutaneous vasculitis fulfilling classification criteria for Henoch-Schönlein purpura (HSP). METHODS: Fifty patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. Patients and ethnically matched controls (n = 117) were genotyped by polymerase chain reaction techniques for a variable-number tandem-repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for any of the individual eNOS polymorphisms were observed between patients fulfilling HSP classification criteria and controls, or when patients were stratified for the presence of nephritis or joint or gastrointestinal manifestations. In the HSP group no linkage disequilibrium between these polymorphisms was found. No significant difference in haplotype frequencies was observed between patients and controls. CONCLUSION: Our results do not support a role for these polymorphisms in the susceptibility to HSP.

Interleukin 8 gene polymorphism is associated with increased risk of nephritis in cutaneous vasculitis.

OBJECTIVE: To assess the influence of interleukin-8 (IL-8), epithelial cell-derived neutrophil-activating peptide (ENA-78), and regulated upon activation normal T cell expressed and secreted (RANTES) gene polymorphisms in the susceptibility and clinical expression of patients fulfilling classification criteria for Henoch-Schönlein purpura (HSP). METHODS: Fifty patients (25 men) from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-8, ENA-78, and RANTES gene polymorphisms. RESULTS: No allele or genotype differences between patients fulfilling HSP classification criteria and controls were observed for any of the chemokines. However, a significantly increased frequency of allele A of the IL-8 gene polymorphism was found in patients with HSP who developed renal manifestations compared with patients without renal involvement (p = 0.02; pcorr = 0.036). Moreover, the genotype distribution in HSP patients with and without renal involvement showed statistically significant differences (p = 0.02). CONCLUSION: In unselected patients with cutaneous vasculitis, carriage of IL-8 allele A influences the susceptibility to renal involvement.

Interleukin 1 receptor antagonist gene polymorphism is associated with severe renal involvement and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of interleukin 1 receptor antagonist gene polymorphism (IL1RN) in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA) and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included if they had a biopsy proven small size blood vessel leukocytoclastic vasculitis limited to skin and also fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1 receptor antagonist intron 2 VNTR polymorphism. RESULTS: We examined 96 Caucasian patients (58 HSP and 38 CLA) and 109 controls. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. We found a significant association between carriage of IL-1 receptor antagonist allele 2 (ILRN*2) and severe renal involvement, manifested as nephrotic syndrome and/or renal insufficiency (p = 0.016), and permanent renal involvement (renal sequelae) (p = 0.012). CONCLUSION: In unselected patients with cutaneous vasculitis, carriage of ILRN*2 alleles influences disease severity rather than susceptibility.

HLA-B35 association with nephritis in Henoch-Schönlein purpura.

OBJECTIVE: To investigate the implications of the HLA-B locus in the susceptibility to Henoch-Schönlein purpura (HSP) and determine if there are associations with renal and gastrointestinal (GI) manifestations of the disease. METHODS: A retrospective study was performed on an unselected population of patients with HSP from Northwest Spain. Forty-eight Caucasian patients (24 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-B genotyped from DNA using molecular based methods. RESULTS: When patients with HSP were compared with matched controls, no differences in HLA-B frequencies were observed. No HLA-B associations with GI manifestations were observed. In contrast, an increased frequency of HLA-B35 was observed in patients with renal manifestations (10 of 31) compared to those without (0 of 17). No significant distortions in frequency were seen for any other HLA-B alleles with HSP subgroups. CONCLUSION: Our results support a role of HLA-B35 in the susceptibility for nephritis in unselected patients with HSP.

Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis exhibit different HLA-DRB1 associations.

OBJECTIVE: To examine the HLA-DRB1 genotype of patients with cutaneous leukocytoclastic angiitis (CLA), a small-sized blood vessel vasculitis limited to skin, and determine if differences exist with Henoch-Schönlein purpura (HSP), a small-sized blood vessel vasculitis with cutaneous and systemic complications. METHODS: A retrospective study was performed on an unselected population of patients from Northwest Spain with primary cutaneous vasculitis classified according to proposed criteria. Patients who fulfilled classification criteria for hypersensitivity vasculitis were included in this study if they had a biopsy proven leukocytoclastic vasculitis limited to skin and, due to this, they also met the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients were included in this study if they had at least 2 years' followup. We studied 96 Caucasian patients (58 HSP, 38 CLA). Patients and ethnically matched controls (n = 145) were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: No HLA-DRB1 genotype differences between patients with CLA and controls were seen. HLA-DRB1*01 was increased and HLA-DRB1*07 reduced in HSP patients compared to controls. When HLA-DRB1 genotypes of patients with CLA and HSP were compared a significant increase of HLA-DRB1*15/16 and especially of HLA-DRB1*07 was observed in the patients fulfilling definitions for CLA compared to those with HSP. CONCLUSION: HSP and CLA exhibit different HLA-DRB1 genotype associations.

Henoch-Schönlein purpura in children and adults: clinical differences in a defined population.

OBJECTIVE: To examine epidemiologic, clinical, and outcome differences between children and adults with Henoch-Schönlein purpura (HSP) in a well-defined population. PATIENTS AND METHODS: Retrospective study of unselected patients with HSP seen at the only referral hospital for the Lugo region of Northwest Spain between 1980 and 2000. Patients were classified according to the criteria proposed by Michel et al. Two well-differentiated age groups were established for comparison: children (under 14 years of age) and adults (over 20 years of age). Also, to assess possible differences in the outcome, only those patients with at least 1 year of follow-up were included in the study. RESULTS: Seventy-three children and 31 adults fulfilled the inclusion criteria described above. Unlike in children, HSP in adults was more common in males. While in children, HSP manifested more commonly in fall and winter, summer and winter were the most common seasons of onset in adults. The frequency of gastrointestinal manifestations was similar in both groups. However, during the course of the disease, 6 of the 31 adults (19%) had severe renal manifestations and another 4 (13%) renal insufficiency. In children, by contrast, the frequency of severe renal manifestations or renal insufficiency during the course of the disease was significantly reduced compared with adults. After 6 years' median follow-up in children, complete recovery was observed in most cases. However, after 5 years' median follow-up, almost 40% of adults had persistent hematuria and 3 of them (10%) renal insufficiency that required hemodialysis in 2 cases. CONCLUSIONS: HSP is generally benign and self-limited in children and more severe in adults.