•An immune-modulator was prepared by concentrating cytokines and growth factors in urine.•It can boost immunomodulatory responses in allergic and autoimmune disease patients.•The immune-modulator is ...administrated sublingually.•This strategy aims to boost the immunomodulatory response of the treated patients.
At “Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C.” in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an “immune-modulator” has been developed. In this study, we will refer to this treatment substance as the “immune-modulator.” In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator.
Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay.
Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1β, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65–70% of samples; IL5, IL-1B, and IL-17 in 50–60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20–30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1β, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment.
The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with an increased prevalence in Mexico. Although its etiology is unknown, its development can be influenced by environmental factors ...such as smoking and viral infections. But among the factors influencing susceptibility, it is the genetic factors that predominate, mainly the HLA-DRB1 genes, and specifically the alleles that have the shared epitope (SE). A transversal study was performed, in which 31 patients (28 women and 3 men) with RA, treated at the autoimmunity clinic of the High Specialty Hospital Ciudad Salud in Tapachula, Chiapas, southern México, were enrolled. Clinical, biochemical, and demographic data were analyzed; ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), RF (rheumatoid factor), and ACPA (anticitrullinated peptide antibody) were recorded. All patients had at least one positive RA biological marker. For HLA alleles frequencies comparison, we enrolled ethnically matched healthy controls in a ratio of 3:1 for 25 cases and 4:1 for 6 cases in order to guarantee the balance between groups regarding the mean of age and proportion of gender (males vs females). HLA-DRB1*04 was found to be significantly increased in patients compared with ethnically matched healthy controls (
p
0.0007, OR: 2.8, 95% CI 1.5–5.1); contrarily, DRB1*08 showed a protective effect (
p
0.005, OR 0.1). This paper confirmed the involvement of HLA genes on risk determination for RA in a population of Mexican Mestizos from Tapachula, Chiapas.
Key Points
•
HLA-DRB1*04 confirms the increased risk of rheumatoid arthritis.
• HLA-DRB1*08 showed a more definite protective effect in southern Mexicans mestizos, a population with more Amerindian ancestry.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of ...more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of
and
could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of
and
are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples.
insertion/deletion polymorphism was evaluated by the high-resolution melting method;
single-nucleotide polymorphism (SNP) (rs4344) and
SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of
gene rs2285666 T/T genotype to critical outcome odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04 and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.
The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors.
genes contain several single nucleotide polymorphisms (SNPs) that confer different ...activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis.
148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS.
Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in
genotype CC had lower levels of ifosfamide (median = 1.8 μmol/l, Q
0.9-Q
4.6) compared with patients with genotype TT + CT (median = 2.8 μmol/l, Q
1.9-Q
5.1),
< 0.001. In the case of the rs2740574 variant in the
gene, patients with normal genotype (TT) presented median = 1.4 μmol/l, (Q
0.7-Q
2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 μmol/l, Q
1.0-Q
4.3),
= 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07-1.59,
= 0.03).
Polymorphisms in
and
genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in
was associated with a worse therapeutic response.
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well-identified as risk factors. SLE patients have ...different phenotypes or clinical presentations, which vary among Mexicans. This variation could be explained by ethnicity and admixture. Since socioeconomic status probably limits and change the patterns of migration, this factor could favor inbreeding and homogamy in some geographic areas. Consequently, it could alter or restrict the possibilities of admixture too. Therefore, the socioeconomic status may also have implications in the susceptibility and the clinical heterogeneity of SLE in Mexican patients.
Methods
One hundred twenty-three SLE patients and 234 healthy individuals with Mexican admixed ancestry were recruited. HLA alleles were analyzed using the HLA typing method based on Sequence-based typing (SBT).
Results
As expected, it was found an increased frequency of the HLA-DRB1*03:01 allele in all socioeconomic groups when compared with healthy individuals. The susceptibility allele found in the low-income SLE patients was HLA-DRB1*04:05 whereas, the susceptibility alleles for the high-income SLE patients were HLA-DRB1*07:01 (pC = 0.03, OR = 2.0) and HLA-DRB1*11:04 (pC = 0.0004, OR = 5.1). Additionally, the frequencies of two protective alleles HLA-DRB1*14:06 (pC = 0.01, OR = 0.28) and HLA-DRB1*16:02 (pC = 0.04, OR = 0.22) were found diminished. These findings correlate with the admixture differences between low-income and high-income SLE patients. The clinical manifestations showed a different distribution between both groups. Arthritis and neurological disorder were prevalent in low-income SLE patients, while the hematological disorder was prevalent in high-income SLE patients.
Conclusions
These findings suggest that HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status. Due to this, the clinical manifestations vary among patients and it could be related to different admixture charge.
Key Point
•
HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status
.
Multiple factors are implicated in the etiology and pathogenesis of Abdominal Aortic Aneurysms (AAA). Available literature of genetic studies has previously suggested the possible roles of ...autoimmunity, genetic predisposition and ethnic susceptibility. Due to the association with autoimmune diseases and proven application in population genetics, we aimed to investigate alleles of the Class II Human Leukocyte Antigens (HLA-DRB1) in the Mexican Mestizo population with aortic aneurysms and determine possible associations with susceptibility.
We performed a case Control Study; the HLA molecular typing was completed for DRB1 loci by LabType Sequence-Specific Oligonucleotide (SSO) SSO-OneLambda kit (Applied Biosystems; Thermo Fisher Scientific. Inc.) in the studied individuals. Allele frequencies (af) were determined, associations were assessed by chi square or fisher exact tests at significance level (< 0.05), and Odds Ratios (OR) were calculated using the STATA software version 14.
The genetic polymorphism of HLA-DRB1 of fifty one patients (70% males with a mean age of 71 years) with atherosclerotic or also known as degenerative AAA were compared with 99 unrelated patients (60% males, mean age 65 years) without the disease Control group (CG) from the same ethnic group. We examined a total of 102 Class II HLA-DRB1 alleles of AAA patients and 198 from CG. When comparing af, we observed the HLA-DRB1*01 af of 0.139 in the AAA compared to 0.05 in the CG p = 0.015, OR 3, 95% confidence interval (CI) 1.29-7.08, the HLA-DRB1*16 af were 0.109 in the AAA and 0.025 in CG (p = 0.006, OR 4.7, 95% CI 1.59-13.98).
Our study confirmed increased frequencies of the alleles HLA-DRB1*01 and HLA-DRB1*16 and their association to the development of AAA in Mexican Mestizo patients. The utility of genetic testing may assist in identifying individuals at genetic risk for the development of this disease in different ethnic groups, who might benefit from earlier ultrasound screening and closer imaging surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different ...clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A
∗
29:02∼C
∗
16:01∼B
∗
44:03∼DRB1
∗
07:01∼DQB1
∗
02:02,
p
C = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.
HLA is a polymorphic antigen presenter which has provided valuable information on the susceptibility of populations to viruses. Therefore, the study of HLA can reveal specific susceptibility or ...resistance alleles to severe COVID-19 in an ethnically dependent manner. This pilot study investigated HLA alleles associated with COVID-19 severity in Tapachula, Chiapas, Mexico. A total of 146 Mexican Mestizos were typed for HLA class I and II using PCR-SSP. The patients were classified according to the outcome (death or improvement) and the infection's severity (mild or severe). In addition, a group of exposed uninfected individuals was included. HLA-A*68 was found to be a protective allele against the severe infection and fatal outcome; pC = 0.03, OR = 0.4, 95% CI =0.20–0.86, and pC =0.009, OR = 0.3, 95% CI =0.13–0.71 respectively. HLA-DRB1*03 also appears to be a protective factor against fatal outcome pC = 0.009, OR = 0.1, 95%IC = 0.01–0.66; however, the low frequency of this allele in the studied population limits the statistical power. The severity and fatal outcome of COVID-19 patients in Tapachula, Chiapas depend more on the lack of resistance than susceptibility HLA alleles.
Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The ...immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers.
High-resolution HLA class II typing was performed using a sequence-based method.
The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC = 0.021, OR = 2.4, 95%CI = 1.19–4.75 and pC = 0.009, OR = 3.4, 95%CI = 1.42–7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC = 0.03, OR = 1.7, IC95% = 1.07–2.76, and a lack of protective alleles carrying aspartic acid70, pC = 0.009, OR = 0.5, IC95% = 0.32–0.84.
The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70–74.
Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives’ risk of developing it.
•The HLA-DRB1∗04:04 and -DRB1∗03:01 are the susceptibility alleles in RA and AITD.•The susceptibility in RA and AITD involves HLA-DRB1 shared epitope alleles.•The Mexican mestizo admixture patterns explain the variety of SE alleles in RA and AITD.•The immunopathogenic mechanism involves lack of DRB1 alleles with aspartic acid at 70 position.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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