scholarly journals Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study

Author(s):  
Rodrigo Roldan-Marin ◽  
Lucia Rangel-Gamboa ◽  
María E. Vega-Memije ◽  
Susana Hernández-Doño ◽  
Daniela Ruiz-Gómez ◽  
...  

Background: Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims: The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods: Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results: Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4–25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7–31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4–10.3. Limitations: The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion: HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

2009 ◽  
Vol 15 (12) ◽  
pp. 1422-1430 ◽  
Author(s):  
Xiao-Mu Wu ◽  
Chaodong Wang ◽  
Kun-Nan Zhang ◽  
Ai-Yu Lin ◽  
Jun-ichi Kira ◽  
...  

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MSassociated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) ( p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) ( p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) ( p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.


2019 ◽  
Vol 3 (2) ◽  
pp. 133-137
Author(s):  
Sergio Mercado Ceja ◽  
◽  
Lucia Rangel Gamboa ◽  
María Elisa Vega Memije ◽  
Angélica Olivo Díaz ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8503-8503
Author(s):  
Y. S. Chun ◽  
Y. Wang ◽  
J. E. Gershenwald ◽  
M. I. Ross ◽  
M. M. Johnson ◽  
...  

8503 Background: Prior reports have suggested a link between specific HLA class II alleles, including HLA-DRB1*1101, and melanoma recurrence. We therefore investigated the relationship between HLA class II alleles and clinical outcome in a large population of patients who presented with localized melanoma. Methods: HLA class II alleles were determined by typing of genomic DNA from patients who presented with localized melanoma (AJCC stage IA-IIC). Patients found to have occult regional disease by sentinel node biopsy were excluded. Log-rank and Cox analysis of outcome versus standard prognostic factors and common HLA class II alleles (=5% of the population) was performed. Results: 1,241 patients underwent HLA typing. The median primary tumor thickness was 1.1 mm, 16% were ulcerated, and the median follow-up was 56 months. Tumor thickness, ulceration, and Clark level were independent predictors of recurrence. The HLA class II allele HLA-DRB1*1101 (11% of the population) independently predicted a higher risk of recurrence [hazard ratio (HR) 2.04, P=0.004] while HLA-DRB1*0401 (20% of the population) predicted a lower risk of recurrence (HR 0.42, P=0.004). HLA- DRB1*1101 was a particularly strong predictor of recurrence in stage I patients (HR 2.73, P<0.0001). Among patients who recurred, HLA- DRB1*1101 was an independent predictor of local-regional vs. distant recurrence (HR 2.7, P=0.007), and was more common in those whose first recurrence was isolated to the regional nodal basin, compared to those whose first recurrence was elsewhere or in multiple locations (24% HLA-DRB1*1101-positive vs. 14%, P<0.009). Conclusions: These results confirm that HLA-DRB1*1101 is a genetic marker of increased risk of melanoma recurrence, while HLA-DRB1*0401 is a marker of decreased risk of recurrence. HLA-DRB1*1101 is a particularly strong marker among the group of patients predicted clinically to be at the lowest overall risk for recurrence, and independently predicts pattern of recurrence (regional nodal failure). This information is of value in the development of surveillance strategies for melanoma patients, as well as the selection, stratification and randomization of early-stage melanoma patients for clinical trials. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20006-e20006 ◽  
Author(s):  
L. Pierret ◽  
S. Wilgenhof ◽  
J. Corthals ◽  
T. Roelandt ◽  
K. Thielemans ◽  
...  

e20006 Background: Ipilimumab (Ipi) is an anti-cytotoxic T lymphocyte associated antigen 4 (CTLA4) IgG1 monoclonal antibody active against metastatic melanoma. Ipi acts by reinforcement of CTL-activation trough B7/CD28 receptor stimulation. A pre- existing anti-tumor CTL repertoire, induced by dendritic cell (DC) vaccination, could influence the therapeutic effect of Ipi. The influence of prior DC-vaccination on the outcome of melanoma patients (pts) treated with Ipi at a single center was analyzed to evaluate this hypothesis. Methods: Data were obtained from the medical files of pts treated at the UZ Brussel with Ipi in protocols CA184–022, -025, and the BMS Ipi medical need program. Ipi (0.3, 3 or 10 mg/kg) was administered iv q3 wks x4 q12 wks thereafter. Results: 20 pts (10M/10F; med age 51y, range 28–72) were identified. Prior therapy: autologous DC-vaccine loaded with melanoma associated antigens (14 pts) ± IFN-a2b (9/14 pts), cytotoxic agents (17 pts). Baseline characteristics: AJCC st IV melanoma (20 pts); baseline LDH > ULN (16 pts). Ipi dose: 0.3 mg/kg (4 pts), 3 mg/kg (2 pts), 10 mg/kg (14 pts). Serial LDH measurements were available for 17 pts; 4 types of LDH-response following Ipi administration were observed: increase (11 pts), decrease (1 pt), fluctuation (4 pts), stable (1 pt). Objective response according to mWHO or irWHO: 3 PR, 1 SD, 16 PD. One pt received 0.3 mg/kg of Ipi (CA184–022) and had SD but no LDH response; at PD she received DC-vaccine and subsequently 10 mg/kg Ipi (medical need program) resulting in a fluctuating LDH-response and regression of an orbita-metastasis. Increasing LDH values following Ipi were less often observed in pts with prior DC-vaccination (5/6 pts (83%) without prior DC-vaccination had increasing LDH-values vs 6/12 pts (50%) with prior vaccination). DC- vaccination also correlated with regression of metastases and disease control (3/15 pts (20%) who were vaccinated had a PR/SD vs 1/6 (17%) PR for those who had not received prior DC-vaccinations). Conclusions: These data represent a small sample size from a single institution; however, our results suggests a potential correlation between prior therapeutic DC vaccination and outcomes in advanced melanoma patients treated with ipilimumab. [Table: see text]


PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51716 ◽  
Author(s):  
Mathilde Bobinet ◽  
Virginie Vignard ◽  
Anne Rogel ◽  
Amir Khammari ◽  
Brigitte Dreno ◽  
...  

2005 ◽  
Vol 154 (2) ◽  
pp. 261-266 ◽  
Author(s):  
D. Planelles ◽  
E. Nagore ◽  
A. Moret ◽  
R. Botella-Estrada ◽  
E. Vila ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Cao ◽  
Li He ◽  
Jingping Ma ◽  
Meiping Chen ◽  
Yiting Li ◽  
...  

Abstract Background This study was performed to investigate clinical features of patients with severe SARS-CoV-2 pneumonia and identify risk factors for converting to severe cases in those who had mild to moderate diseases at the start of the pandemic in China. Methods In this retrospective, multicenter cohort study, patients with mild to moderate SARS-CoV-2 pneumonia were included. Demographic data, symptoms, laboratory values, and clinical outcomes were collected. Data were compared between non-severe and severe patients. Results 58 patients were included in the final analysis. Compared with non-severe cases, severe patients with SARS-CoV-2 pneumonia had a longer: time to clinical recovery (12·9 ± 4·4 vs 8·3 ± 4·7; P = 0·0011), duration of viral shedding (15·7 ± 6·7 vs 11·8 ± 5·0; P = 0·0183), and hospital stay (20·7 ± 1·2 vs 14·4 ± 4·3; P = 0·0211). Multivariate logistic regression indicated that lymphocyte count was significantly associated with the rate of converting to severe cases (odds ratio 1·28, 95%CI 1·06–1·54, per 0·1 ×  109/L reduced; P = 0·007), while using of low-to-moderate doses of systematic corticosteroids was associated with reduced likelihood of converting to a severe case (odds ratio 0·14, 95%CI 0·02–0·80; P = 0·0275). Conclusions The low peripheral blood lymphocyte count was an independent risk factor for SARS-CoV-2 pneumonia patients converting to severe cases. However, this study was carried out right after the start of the pandemic with small sample size. Further prospective studies are warranted to confirm these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029839. Registered 15 February 2020 - Retrospectively registered.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Muhammad H Niazi ◽  
Mohammad El-Ghanem ◽  
Kevin Cockroft ◽  
Kathy Morrison ◽  
Alicia Richardson ◽  
...  

Background: Prehospital triage tools are essential to identify large vessel occlusion (LVO) in order to triage patients to a comprehensive stroke center for timely endovascular treatment (ET). Prehospital Acute Stroke Severity Scale (PASS) (score range 0-3) was recently identified as a valuable tool to predict LVO. Several studies have shown that in patients treated with IV tPA, a score calculated by multiplying admission NIHSS by the time from symptom onset to tPA treatment (in hours) can predict outcome. In our study, we applied similar concept for patients with LVO who underwent successful ET. Methods: We retrospectively reviewed all LVO patients between January 2015 and June 2016 who received ET. We analyzed the association of time of symptom onset to groin time (OGT), NIHSS, PASS, NIHSS-OGT, and PASS-OGT with modified Rankin scale (mRS) at the time of discharge. Results: Fifty-four patients underwent ET during the study period. Patients with posterior circulation LVO and those treated after 6 hours from last known normal were excluded. A total of 34 patients were left for final analysis. Patients with a good outcome (mRS ≤2) had an average NIHSS-OGT score of 43.2 (95% CI: 29.7-56.8) and PASS-OGT score of 5.52 (95% CI: 4.48-6.56). Patient’s with poor to miserable outcomes (mRS 3-6) average NIHSS-OGT 84.7 (95% CI: 72.8-96.6) and PASS-OGT average 9.8 (95% CI: 8.3-11.2). For NIHSS-OGT cut off of 55 the sensitivity and specificity was 0.75 and 0.85 respectively; diagnostic odds ratio 16.5 (96% CI: 2.41-112.83). For PASS-OGT cut off of 6.5 the sensitivity and specificity were 0.88 and 0.76 respectively; diagnostic odds ratio 23.33 (95% CI: 2.37-229.33). The wide confidence intervals can be attributed to small sample size. Conclusion: Our study indicates NIHSS–OGT and PASS-OGT scores have a linear relationship with discharge mRS and can reliably predict early clinical outcomes after ET. Further confirmation with randomized control trials is needed.


2004 ◽  
Vol 53 (6) ◽  
pp. 551-559 ◽  
Author(s):  
Selma Ugurel ◽  
Dario Uhlig ◽  
Claudia Pf�hler ◽  
Wolfgang Tilgen ◽  
Dirk Schadendorf ◽  
...  

2018 ◽  
Vol 4 (4) ◽  
pp. e257 ◽  
Author(s):  
Kotaro Ogaki ◽  
Michael G. Heckman ◽  
Shunsuke Koga ◽  
Yuka A. Martens ◽  
Catherine Labbé ◽  
...  

ObjectiveThe triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA.MethodsA total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series.ResultsWe identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79%), 1 patient with clinically diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034).ConclusionsOur preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.


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