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Biomedical subjects

K Reich

Publications and source records attributed to K Reich.

At least 19 recordsLinked to original sources
PubMed2006

[Evidence-based therapy of Raynaud's syndrome].

Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite its high frequency, the majority of available therapies have not been validated in randomized controlled trials. Effective therapies with a high level of evidence include the calcium channel blocker nifedipine. As analyzed by meta-analyses, nifedipine showed improvement of the peripheral circulation, as well as reduction of both the intensity and frequency of attacks in patients with primary and secondary Raynaud's syndrome as compared to placebo. Similar results in a metaanalysis were obtained for intravenous infusions of iloprost in patients with secondary Raynaud's phenomenon associated with systemic sclerosis. In addition, intravenous infusions of iloprost improved healing of fingertip ulcers in patients with systemic sclerosis. Therapies with significant effects in single randomized controlled trials include angiotensin II-receptor type 1 antagonists (losartan), the calcium channel blockers felodipine und amlodipine, serotonin-reuptake-inhibitors (fluoxetine) und phosphodiesterase-V-inhibitors (sildenafil, vardenafil). However, the results for these promising substances have to be confirmed in long-term trials with larger patient numbers.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Improvement in quality of life with infliximab induction and maintenance therapy in patients with moderate-to-severe psoriasis: a randomized controlled trial.

BACKGROUND: Psoriasis has a well-documented, markedly negative effect on patient quality of life. OBJECTIVES: To evaluate the impact of long-term infliximab maintenance therapy on health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The Dermatology Life Quality Index (DLQI) and 36-item Short Form Health Survey (SF-36) were administered as part of the pivotal double-blind, placebo-controlled efficacy and safety EXPRESS study of infliximab in chronic plaque psoriasis. In total, 378 patients with moderate-to-severe psoriasis were enrolled at 32 centres in Europe and Canada. Patients were randomized to receive either placebo or infliximab 5 mg kg(-1) induction at weeks 0, 2 and 6 followed by maintenance every 8 weeks; placebo patients crossed over at week 24 to receive the infliximab induction and maintenance regimen. RESULTS: At week 10, infliximab-treated patients had significantly greater improvement in DLQI scores (P < 0.001) and SF-36 physical and mental component summary scores (P < 0.001) than placebo-treated patients. Significant improvement (P < 0.001) was also seen in all eight SF-36 subscales, and was greatest for the "Bodily Pain" and "Social Functioning" scales. Significant improvement in HRQoL persisted with maintenance infliximab treatment at week 24 (P < 0.001), with patients achieving a Psoriasis Area and Severity Index score of 0 reporting the greatest benefit. Treatment-related HRQoL improvement remained substantial at week 50. CONCLUSIONS: Infliximab induction and maintenance regimens resulted in rapid, substantial, sustained and clinically meaningful improvement in both dermatology-specific and general quality of life indices in patients with psoriasis, with total clearance resulting in maximum improvement.

Adult↗
PubMed2006

Who is really in control of skin immunity under physiological circumstances - lymphocytes, dendritic cells or keratinocytes?

Our views of the skin immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and skin biology, but also have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as 'lead actors' on the skin immunity stage, the lowly keratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate skin immunity system, which may control even acquired skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as 'stage managers' pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance - complete with the impresario's overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talents and even the critic's digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play - at least for the time being...

Dendritic Cells↗
PubMed2006

Cost of moderate to severe plaque psoriasis in Germany: a multicenter cost-of-illness study.

BACKGROUND: There is little information concerning the costs of psoriasis and patients' quality of life (QoL) in Germany. OBJECTIVE: To obtain data on the annual costs and QoL(to follow in a further publication) of patients with moderate to severe plaque psoriasis. METHODS: Between October 2003 and February 2004, six office-based dermatologists and eight dermatology outpatient departments retrospectively documented cost-of-illness data from a societal cost perspective in 184 patients over a 12-month period. Patients were stratified into three subgroups according to their treatment scheme. RESULTS: Mean total costs amounted to euro 6,709 per patient and year. The mean PASI score was 18.2 and PBSA 28.9%. Annual costs were highest with euro 8,831 in high-need patients. They also showed the highest PASI score (22.2). CONCLUSION: Moderate to severe plaque psoriasis is associated with tremendous costs, particularly in patients not adequately controlled by conventional therapies, while the outcomes of patients were unsatisfactory.

Adult↗
PubMed2005

Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients.

INTRODUCTION: Variant R620W of protein tyrosine phosphatase non-receptor type 22 (PTPN22) has consistently been reported as a susceptibility factor for several autoimmune diseases. We investigated its role in susceptibility to psoriasis, the relevance of possibly other disease-causing variants, and interdependency of the major risk factor for psoriasis at PSORS1. METHODS: R620W was tested in a case-control study initially with 375 German patients and then with an enlarged sample of an additional 418 patients. Analyses were extended to linkage disequilibrium (LD) based haplotypes. Potential interaction between risk haplotypes of PTPN22 and the PSORS1 associated risk allele was tested by regression analysis. PTPN22 coding sequence was determined in 20 patients carrying the risk haplotype. Association and regression analysis were also performed in the extended case-control study. RESULTS: R620W was not associated in either case-control study, while significant association (corrected for multiple testing) with one haplotype (C-4) of the LD block encompassing PTPN22 as well with another haplotype (B-3) within an adjacent telomeric LD block was detected. No evidence for interaction between risk haplotype C-4 and the PSORS1 associated risk allele was found. Sequencing excluded other coding variants within PTPN22 as a basis for association findings. Analysis of the extended study group confirmed association for haplotypes B-3 and C-4 and independence of risk haplotypes C-4 and PSORS1. DISCUSSION: We exclude a major role of *620W in German psoriasis patients but suggest that other susceptibility determinant(s) within non-coding regions of PTPN22 or its proximity might exist acting independently of the major PSORS1 risk factor.

Alleles↗
PubMed2005

[Infliximab. Role in the treatment of psoriasis].

Psoriasis is one of the immune-mediated inflammatory diseases (IMIDs), in whose pathogenesis Th1-mediated immune responses are considered crucial. Infliximab is a chimeric monoclonal antibody directed against the Th1-cytokine TNF-alpha that has already been approved for the therapy of psoriatic arthritis (in combination with methotrexate). In clinical studies, infliximab has proved safe and effective in treating plaque-type psoriasis. In 80% of treated patients, the Psoriasis Area and Severity Index (PASI) decreased after 10 weeks by > or =75%. Infliximab is expected to be approved as second-line therapy in Germany this year for the treatment of psoriasis vulgaris.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

A close look at autoimmune muscle disorders: association of Lambert-Eaton myasthenic syndrome with dermatomyositis.

Dermatomyositis/polymyositis (DM/PM) and Lambert-Eaton myasthenic syndrome (LEMS) are two autoimmune disorders that have very rarely been reported to occur together in the same patient. We report on two patients with DM who were later diagnosed with concomitant LEMS, and point out diagnostic challenges in identifying LEMS in patients with DM/PM. As specific treatment for LEMS is available, it is important to identify those DM/PM patients who suffer from concomitant LEMS.

Comorbidity↗
PubMed2004

Granulocyte colony-stimulating-factor-induced psoriasiform dermatitis resembles psoriasis with regard to abnormal cytokine expression and epidermal activation.

Psoriasis is a chronic inflammatory skin disorder characterized by accumulation of Th1-type T cells and neutrophils, regenerative keratinocyte proliferation and differentiation, and enhanced epidermal production of antimicrobial peptides. The underlying cause is unknown, but there are some similarities with the immunologic defense program against bacteria. Development of psoriasiform skin lesions has been reported after administration of granulocyte colony-stimulating factor (G-CSF), a cytokine induced in monocytes by bacterial antigens. To further investigate the relation between this type of cytokine-induced dermatitis and psoriasis, we analyzed the cutaneous cytokine profile [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), IL-12p35 and p40, and IL-8] and expression of markers of epidermal activation [Ki-67, cytokeratin-16, major histocompatibility complex (MHC) class II, intercellular adhesion molecule-1 (ICAM-1)] in a patient who developed G-CSF-induced psoriasiform dermatitis by using quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistology. The histologic picture resembled psoriasis with regard to epidermal hyperparakeratosis and the accumulation of lymphocytes in the upper corium. CD8(+) T cells were found to infiltrate the epidermis which was associated with an aberrant expression of Ki-67, cytokeratin-16, MHC class II, and ICAM-1 on adjacent keratinocytes. As compared to normal skin (n = 7), there was an increased expression of TNF-alpha, IL-12p40, and IL-8, a decreased expression of TGF-beta1, and a lack of IL-10, similar to the findings in active psoriasis (n = 8). Therefore, G-CSF may cause a lymphocytic dermatitis that, similar to psoriasis, is characterized by a pro-inflammatory Th1-type cytokine milieu and an epidermal phenotype indicative of aberrant maturation and acquisition of non-professional immune functions.

Cytokines↗
PubMed2003

Cytokine gene polymorphisms in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders characterized by abnormal cytokine production. From association studies there is evidence that functionally relevant cytokine gene polymorphisms contribute to the genetic basis of psoriasis. Association studies in AD have mostly been limited to polymorphisms of T-helper 2-type cytokines, which dominate in acute AD lesions. Unexpectedly, the results of recent genome scans indicate linkage of AD to psoriasis susceptibility loci. Therefore, AD may also be influenced by genes that modulate cutaneous inflammation independently from atopic mechanisms. OBJECTIVES: To investigate further the role of cytokine gene polymorphisms in AD. METHODS: Polymorphisms in the genes encoding tumour necrosis factor-alpha (TNFA-238 G/A, -308 G/A), interleukin (IL)-1beta (IL1B-511 T/C, +3953 T/C), IL-6 (IL6-174 C/G), IL-10 (IL10-1082 A/G) and the IL-1 receptor antagonist (IL1RN intron 2) were investigated in German patients with AD (n = 94) and in healthy nonatopic individuals (n = 214) by polymerase chain reaction-based methods and direct cycle sequencing. RESULTS: No association was found between AD and any of the polymorphisms analysed. This is in contrast to the recently described association between psoriasis and the TNFA-238 and IL1B-511 polymorphisms. CONCLUSIONS: Our data indicate that cytokine gene polymorphisms may act as specific markers of inflammatory skin diseases rather than contribute to a general disposition towards cutaneous inflammation.

Adolescent↗
PubMed2001

Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.

Caspase 1↗
PubMed2001

Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn's disease.

Recruitment of lymphocytes is a prominent feature of the inflammatory process in Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotactin (Lptn) as a potential regulatory factor for the recruitment of T cells in CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflammation by real-time quantitative reverse transcriptase-polymerase chain reaction and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to normal controls Lptn mRNA was significantly increased in tissue samples affected by CD. Cells expressing Lptn were identified as T cells, mast cells, and unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T cells isolated from peripheral blood, which could be prevented by dexamethasone, cyclosporine A, and FK506. A similar regulation mechanism could be identified for the Lptn receptor GPR-5 in peripheral T cells. In addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cells. The results indicate that local expression of Lptn by activated T cells and to a lesser extent by mast cells and dendritic cells represents a key regulator for lymphocyte trafficking and maintenance of the inflammatory process observed in CD, which might be partly mediated through an autocrine/paracrine pathway of activated T cells.

Cell Differentiation↗
PubMed2001

Response of psoriasis to interleukin-10 is associated with suppression of cutaneous type 1 inflammation, downregulation of the epidermal interleukin-8/CXCR2 pathway and normalization of keratinocyte maturation.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Cell Differentiation↗
PubMed2001

Interleukin 16 expression and phenotype of interleukin 16 producing cells in Crohn's disease.

BACKGROUND: The mechanisms involved in the initiation and maintenance of Crohn's disease are poorly understood. Previous studies have demonstrated an increased number of infiltrating CD4+ T cells within the inflammatory affected bowel wall in Crohn's disease. Novel therapy approaches using anti-CD4 antibodies are thought to be effective in Crohn's disease. AIMS: Interleukin 16 (IL-16) has been characterised as a chemokine with selective chemoattraction for CD4+ inflammatory T cells. In this study, cellular expression of IL-16 in Crohn's disease and ulcerative colitis was investigated. METHODS: Expression of IL-16 was analysed in tissue samples of Crohn's disease, ulcerative colitis, and normal controls by applying reverse transcription-polymerase chain reaction, non-radioactive in situ hybridisation, and immunohistochemistry. Double staining methods were used to characterise cells expressing IL-16. The amount of infiltrating CD4+ cells was determined by immunohistochemistry and correlated with the corresponding IL-16+ cell number by step sections. RESULTS: An increased number of IL-16+ cells in Crohn's disease in comparison with ulcerative colitis and control probes was demonstrated. IL-16 was expressed by CD4 and CD8 positive T cells. In addition, in active Crohn's disease there was a substantial number of IL-16 positive mast cells. The increased number of CD4+ lymphocytes correlated positively with the increased number of IL-16 positive cells in Crohn's disease. CONCLUSION: Our results demonstrate that increased expression of IL-16 in T cells and mast cells in active Crohn's disease is associated with increased numbers of CD4+ lymphocytes. Local expression of IL-16 seems to play a significant role in the initiation and persistence of the inflammatory process in Crohn's disease, presumably by IL-16 mediated recruitment of CD4+ cells, mostly lymphocytes, into the bowel wall.

Adolescent↗
PubMed2001

Water quality assessment for indirect potable reuse: a new methodology for controlling trace organic compounds at the West Basin Water Recycling Plant (California, USA).

The West Basin Water Recycling plant (California; USA) was built to increase the region's water resource availability. The plant influent is produced at Los Angeles Hyperion wastewater treatment plant and is treated through two parallel treatment processes depending on the end use: (1) Title 22 water for industrial and urban use, and (2) barrier treatment for groundwater recharge. A new methodology was applied to monitor the fate of base neutral compounds in the water barrier treatment train. The methodology included large sample volumes coupled with integrated chromatographic analysis (ICA). Data indicated a 25% increase in concentration of base neutral compounds after RO pretreatment, followed by a 70% removal efficiency after RO. The increase in concentration after RO pretreatment appears to be linked to the use of lime clarification.

Calcium Compounds↗
PubMed2000

Rapid quantitation of proinflammatory and chemoattractant cytokine expression in small tissue samples and monocyte-derived dendritic cells: validation of a new real-time RT-PCR technology.

The analysis of cytokine profiles plays a central part in the characterization of disease-related inflammatory pathways and the identification of functional properties of immune cell subpopulations. Because tissue biopsy samples are too small to allow the detection of cytokine protein, the detection of mRNA by RT-PCR analysis is often used to investigate the cytokine milieu in inflammatory lesions. RT-PCR itself is a qualitative method, indicating the presence or absence of specific transcripts. With the use of internal or external standards it may also serve as a quantitative method. The most widely accepted method is quantitative competitive RT-PCR, based on internal shortened standards. Recently, online real-time PCR has been introduced (LightCycler), which allows quantitation in less than 30 min. Here, we have tested its use for the analysis of cytokine gene expression in different experimental in vitro and ex vivo settings. First, we compared quantitative competitive RT-PCR with real-time RT-PCR in the quantitation of transcription levels of the CD4(+) cell-specific chemoattractant Interleukin-16 during the maturation of monocyte-derived dendritic cells, and found a good correlation between both methods. Second, differences in the amounts of IL-16 mRNA in synovial tissue from patients with rheumatoid arthritis and osteoarthritis as assessed by real-time RT-PCR paralleled differences in the level of IL-16 protein in the synovial fluid. Finally, we employed real-time RT-PCR to study the cutaneous expression of several cytokines during experimental immunomodulatory therapy of psoriasis by Interleukin-10, and demonstrate that the technique is suitable for pharmacogenomic monitoring. In summary, real-time RT-PCR is a sensitive and rapid tool for quantifying mRNA expression even with small quantities of tissue. The results obtained do not differ from those generated by quantitative competitive RT-PCR.

Arthritis, Rheumatoid↗
PubMed2000

Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization.

OBJECTIVE: Thimerosal is an important preservative in vaccines and ophthalmologic preparations. The substance is known to be a type IV sensitizing agent. High sensitization rates were observed in contact-allergic patients and in health care workers who had been exposed to thimerosal-preserved vaccines. There is evidence for the involvement of the glutathione system in the metabolism of thimerosal or its decomposition products (organomercury alkyl compounds). Thus detoxification by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1 might have a protective effect against sensitization by these substances. METHODS: To address this question, a case control study was conducted, including 91 Central European individuals with a positive patch-test reaction to thimerosal. This population was compared with 169 healthy controls and additionally with 114 individuals affected by an allergy against para-substituted aryl compounds. The latter population was included in order to test whether possible associations were due to substance-specific effects, or were a general feature connected with type IV immunological diseases. Homozygous deletions of GSTT1 and GSTM1 were determined by polymerase chain reaction. RESULTS: Glutathione S-transferase M1 deficiency was significantly more frequent among patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy control group (49.1%) and the "para-compound" group (48%, P = 0.034). Glutathione S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely elevated versus healthy controls (16.0%) and the "para-compound" group (14.0%). The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal-sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in the "para-compound" group (17.6% vs. 6.1%, P =0.014), revealing a synergistic effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1 negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1], GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]). CONCLUSIONS: Since the glutathione-dependent system was repeatedly shown to be involved in the metabolism of thimerosal decomposition products, the observed association may be of functional relevance.

Adolescent↗
PubMed2000

N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy.

Sensitization to arylamines such as p-phenylenediamine is frequently diagnosed in patients with allergic contact dermatitis. Reactive metabolites of p-phenylenediamine might be produced in the skin by O-acetylation of N-hydroxylamines catalysed by local N-acetyltransferases (NATs). In this study, we tested whether genetic polymorphisms of NATs, which are known to affect enzyme activity, may influence the susceptibility to para-substituted arylamine-induced contact eczema. Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was investigated in 88 patients sensitized to para-substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 wild-type allele, were more common in the contact allergy (44%) than in the healthy control group [30%; P = 0.042, odds ratio 1.9 (95% confidence interval, CI 1. 05-3.27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype were significantly less frequent among patients [13% vs. 38% in controls; P = 0.009, odds ratio 0.39 (95% CI 0.19-0.78)]. The carriage rate of the NAT1*10 allele, which is supposed to encode for a rapid NAT1 phenotype, was not significantly different between patients and controls [43% vs. 36%; odds ratio 1.5 (95% CI 0.88-2.68)]. Interactions between NAT2*4 and NAT1*10 were suggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in patients (27%) compared with controls [15%; P = 0.039, odds ratio 2.1 (95% CI 1.04-4.04)]. As the NAT1 and NAT2 encoding genes are located in close proximity on chromosome 8p22, the latter finding could at least partly be due to genetic linkage. In fact, a linkage disequilibrium between NAT2*4 and NAT1*10 was observed in the contact allergy (P = 0.0025) and in the control group (P = 0.042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to para-substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.

Adolescent↗