• Nu S-Au Găsit Rezultate

View of Association of Tumor Necrotic Factor Alpha Gene Single Nucleotide Polymorphism in Rubella Vaccine Response

N/A
N/A
Protected

Academic year: 2022

Share "View of Association of Tumor Necrotic Factor Alpha Gene Single Nucleotide Polymorphism in Rubella Vaccine Response"

Copied!
13
0
0

Text complet

(1)

Association of Tumor Necrotic Factor Alpha Gene Single Nucleotide Polymorphism in Rubella Vaccine Response

Mohammed J. Hamed1, Haidar S. Kadhim2

1Department of Microbiology, College of Medicine, AL-Nahrain University, Iraq, Email:

[email protected]

2Ph.D Department of Microbiology, College of Medicine, AL-Nahrain University, Iraq, Email:

[email protected] Abstract:

Background:Rubella virus is a mild, acute, contagious disease. Rubella usuallyoccurs in young adults and in children, and mainly transmitted by respiratory route. Pregnant women infected with rubella can transmit infection to their offspring. Congenital rubella cause serious infection include miscarriage, stillbirth, asymptomatic infection in the newborn and /or Congenital Rubella Syndrome (CRS).

Objective: To detected level of Immune response to Rubella virus vaccine among vaccinated children and to investigate is the single nucleotidepolymorphisms(SNP) inTumor Necrotic Factor Alpha (TNF-α gene)are associated with variations in response to rubella.

Methods: This is a cross-sectional study, a total of 180 hospitalized children age between (6-8) years were included, who are previously vaccinated with two doses ofmeasles-mumps-rubella vaccine )MMR(vaccine. All samples were collected from the unit of blood collection in the Central Teaching Hospital of pediatric in Baghdad/Al-Iskan during the period from October 2019 to January 2020.Level of Immune response of IgG antibody detected by enzyme linked immunosorbent assay (ELISA), SNP in TNF-αgene detection by allele- specific polymerase chain reaction(PCR).

Result:The number of children who had low immune response was 33,moderate immune response was 103 and the children with high immune response was 44 with percentages 18.34,57.22% and 24.44% respectively.

Female was slightly high percentage with low immune response with 19% than male with17.8% ,while male has high percentage of high immune response with 25.7% than female with 22.8% with no significant difference.The percentage of low immune response is more in age 6 and 8 years than 7 years with percentage of 18.8% and 18.7% respectively.

Conclusions:MMR vaccine is important especially in female to avoid congenital infection Age may effect on immune response of MMR vaccine.There is an association between SNP in TNF-α gene and Rubella vaccine immune response.

Keywords: Rubella, TNFA, SNP, MMR.

Introduction

Rubella is a viral disease that usually causes a mild, acute, self-limited disease, affects both children and young adults with rare complications. However, the major public health infection with rubella in early pregnancy lead to the teratogenic effect. Early infections during pregnancy may lead to fetal death, miscarriage, or a birth of a child with Congenital Rubella Syndrome (CRS). Infants with CRS may have intellectual disability, heart defects, sensorineural hearing loss, or ocular abnormalities (1, 2).

Complication with rubella might be happening in adult and adolescent such as arthritis, arthralgia and thrombocytopenic purpura. Rubella encephalitis uncommon but may occur in children (3).

Diagnosis of rubella virus in a laboratory can be detected either serology; when positive IgM present it means an acute infection, in case there is a four-fold increase in IgG it means patient in convalescent state or detection by polymerase chain reaction (PCR) (4).

(2)

Rubella infection is a vaccine-preventable disease, vaccination with MMR (mumps, measles, rubella) vaccine is available in most of the countries to prevent rubella infection and reduce the incidence of rubella infection mainly to prevent congenital rubella syndrome. Both natural infection and immunization with rubella vaccine give lifelong immunity (5,6).

Rubella vaccine is given as a single component but occasionally as a combination with measles, mumps and rubella (MMR) vaccine (7). These vaccines are very effective to provide a protective immunity against rubella infection more than 95% in recipients individual and more than 99%

after two doses. (8,9). In spite of this highly effective ratio of vaccination but the infection still occur and more importantly infect with Congenital Rubella Syndrome cause a serious health problem due to the teratogenic effects and risk of miscarriage and stillbirth, particularly when the mother becomes infected during the first trimester of pregnancy (3,10-12).

One of these reasons that make an individual not responding to the MMR vaccine is genetic polymorphisms. Response to the vaccine is associated with genetic polymorphisms include polymorphism in HLA (human leukocyte antigen), cytokines, as well as in cytokine receptor genes, antiviral gene, vitamin receptor and other genes (13). The front-line antiviral cytokine is Tumor necrotic alpha (TNF-α) which acts as a trigger for “innate immune pathways” and IL-6 is the critical “immunological switch” that leads to progress the innate host immune system towards an adaptive response (14-16).

Tumor necrotic alpha (TNF-𝛼) is a proinflammatory cytokine produced by many cell type includes macrophages, monocytes, T cells, neutrophils, and NK-cells (natural killer cell). TNF-𝛼 involved in the regulation of many essential cellular processes such as differentiation, proliferation, immune response, and growth (17).

Methods:

This is a cross-sectional study, a total of 180 hospitalized children age between (6-8) years will be included, who are previously vaccinated with two doses of )MMR ( vaccine. exclusion criteria include patient previously infected with rubella, patient with Nephrotic syndrome, patient on immune-suppressant agents, patient with chemotherapy and patient with allergy. This study under the agreement of the ethical approval of the Institutional Board Review (IRB) in the College of Medicine, Al-Nahrain University under the No. 240 in 2019 /7/30.All sample from vaccinated children include 4 ml of the leftover blood sample will be collected from each child, two ml were collected in tubes with EDTA for extraction of DNA and allele-specific PCR, the other two ml were collected into plain tubes in which serum was taken from there for ELISA to detect IgG antibody level of Rubella. Kit used for ELISA detection designed by (Demeditec diagnosis, Germany) while DNA extraction done by using DNA extraction kit (Geneaid Biotech, Taiwan). To detect TNFA gene SNP in childrenvaccinated with MMR allele specific PCR were used.Primer of TNFA gene was designed by using online data tools to detect TNFA SNP in target DNA. Oligonucleotide synthesis by scientific researcher CD.ltd.diwaniyah city center as show in table (1).

(3)

Table (1): primer used in PCR:

Gene Primer sequence (5’----3’) Product size (bp)

Fw1:GGAAGAGGGCTCAAGGTTAGG

TNFA Fw2:GGAAGAGGGCTCAAGGTTAAG 510 bp

(rs2256974) Fw3:GGAAGAGGGCTCAAGGTTATG

Rp : CTCAGGGTTGGCACATAAGG Result:

A total of 180 samples of previously vaccinated children included in this study. The number of children who had low immune response were 33 with 18.34 %. While the children with moderate immune response were 103 with 57.22% and the children with high immune response were 44 with 24.44%. Although there are no significant differences but moderate immune response shows higher immune response with 57.22% as seen in the table (2).

Table (2): Rubella vaccine immune response invaccinated children.

Rubella IgG response

No. % Mean Std.

Deviation

Minimum Maximum P value

Low 33 18.34% 7.03 0.92 6.00 8.00 0.428

Moderate 103 57.22% 6.97 0.90 6.00 8.00 High 44 24.44% 7.18 0.87 6.00 8.00 Total 180 100.00% 7.03 0.89 6.00 8.00 NS: non-significant p value <0.05

The number of vaccinated female is 79 while number of vaccinated male was 101. Higher percentage of immune response of female seeninmoderate immune responsewith 58.2%, while higher percentage of immune response of male seen in high immune response with 25.7%.

Inspire of there is non-significant difference but the mean of IgG level immune response is higher in male with 175.91% as shown in the table (3)

Table (3): Association between Rubella vaccine immune response and sex.

Rubella IgG response Sex P value

Male Female

Low Count 18 15 0.897NS

% 17.8% 19.0%

(4)

Moderate Count 57 46

% 56.4% 58.2%

High Count 26 18

% 25.7% 22.8%

IgG level (IU/ml) Male Female P value

Mean 175.91 170.77 0.744NS

Standard Deviation 181.14 183.26

Median 126.40 107.90

Percentile 25 30.90 28.50

Percentile 75 253.60 236.30

NS: non-significant p value <0.05

In this study, 3 age groups of children were included which is 6,7 and 8 years. The percentage of low immune response is more in age 6 and 8 years than 7 years with percentage of 18.8% and 18.7% respectively. In moderate immune response the age of 6 years was the high percentage with 62.3%. The age of 8 years has high percentage 28% with high immune response. Although there is no significant difference the mean of immune response with 7 years’ age is higher with 190.20 IU/ml as shown in table (4)

Table (4): Association between Rubella vaccine immune response and age

Age P value

6 years 7 years 8 years

Rubella IgG response

Low

Count 13 6 14 0.729 NS

% 18.8% 16.7% 18.7%

Moderate

Count 43 20 40

% 62.3% 55.6% 53.3%

High Count 13 10 21

% 18.8% 27.8% 28.0%

IgG level IU/ml

Mean 153.55 190.85 183.90 0.818 NS

Standard Deviation 154.36 205.40 193.08

Median 107.90 109.20 143.40

Percentile 25 28.50 27.75 30.90 Percentile 75 211.20 351.60 261.80 NS: non-significant p value <0.05

(5)

The number of children who had homozygous wild type(GG) is 163, the number of heterozygous mutant (TG or AG) was 8 and the number of homozygous mutant (AA or TT) was 9. Although non-significant difference the homozygous wild type had high percentage of moderate and high immune response with 57.7% and 24.5% respectively with mean 174.44IU/ml.

Table (5): Association between Rubella vaccine immune response and genotyping of TNF-α gene.

Genotype

Total Homozygous

Wild (GG)

Heterozygous Mutant (TG or AG)

Homozygous Mutant (AA or TT)

Rubella IgG response

Low 29 2 2 33

% 17.8% 25.0% 22.2%

Moderate 94 3 6 103

% 57.7% 37.5% 66.7%

High 40 3 1 44

% 24.5% 37.5% 11.1%

Total 163 8 9 180

IgG level IU/ml

Mean 174.44 207.89 128.99

0.428NS Standard

Deviation 181.63 255.55 95.73

Median 121.80 103.80 134.40

Percentile 25 29.00 18.35 62.60

Percentile 75 244.10 335.35 177.20

NS: non-significant p value <0.05

The result shows significant difference between wild allele and mutant2 allele (M2) (p<0.05), the percentage of immune response was higher in M2 with low immune response with 33.33% and moderate immune response with 61.11% than in wild allele which was 18.02% in low immune response and 57.36% in moderate immune response,while the percentage of high immune response was higher in wild allele with 24.62 % than in M2 with 5.56%. Also the wild allele has higher mean with 174.97 as compared to M2 with mean 89.58. The result also shows significant difference between mutant 1 allele(M1) and wild allele, wild allele has high moderate immune response with 57.36% than in M1 with 44.44% as show in table (6).

(6)

Table (6): Association between Rubella vaccine immune response and allele of TNF-α.

Allele

WILD (333)

MUTANT1 (9)

MUTANT2 (18)

Rubella IgG response

Low 60 0 6

% 18.02% 0.00% 33.33%

Moderate 191 4 11

% 57.36% 44.44% 61.11%

High 82 5 1

% 24.62% 55.56% 5.56%

P value 0.034*

IgG level (IU/ml)

Count 333 9 18

Mean 174.97 293.17 89.58

Standard

Deviation 183.23 175.16 95.90

Median 121.80 266.00 73.30

Percentile 25 29.00 197.30 12.10

Percentile 75 244.10 309.60 134.40

P value

W vs M1 0.015*

W vs M2 0.040*

M1 vs M2 0.001**

*: statistical significance (p<0.05)

**: high statistical significance (p<0.001)

(7)

Figure (1): Gel electrophoresis for genotyping of TNF-α gene (PCR product). In lanes1,3:

heterozygous mutant (TG) while the lanes 7homozygous wild type (GG) with ladder 100-1000 bp.

Figure (2): gel electrophoresis of TNF-α gene PCR product, mutant1 allele in lanes 2 with 510 bp.

(8)

Figure (4-4): Gel electrophoresis of TNF-α genePCR product. mutant2 allele in the lanes 1 with 510 bp.

Discussion:

The rubella virus infection immune response and attenuated vaccines of rubella virus, depending on many factors including age, genetics and sex (18).

One of the most dangerous sequels of failure vaccine is Congenital Rubella Syndrome (CRS) the main cause of severe defects in infants. When a woman in early pregnancy infected with the rubella virus, she has a chance of 90% passing the rubella virus to her fetus (19).

The current study of 180 samples of previously vaccinated children aged between 6-8 years.

The percentage of children who had a low immune response is 18.34%, while the children with moderate immune response are 57.22% and the children with a high immune response are 24.44%. The result showed the percentage of low immune response is more in age 6 and 8 years than 7 years with a percentage of 18.8% and 18.7% respectively. This result is in accordance with Al-Musawi and Hasony in 2007 the study included a total of 1309 blood samples,1232 samples were collected from children aged between 1 month to 14 years in Basrah governorate.

They showed the seropositivity of the highest proportion (71.2%) was observed among children aged 1-2 years who received the vaccine before sampling, then declined post-vaccination in ages 3-4, 5-6 years to 68.1% and 58.5% respectively, to reach after 7-8 years its lowest level (48.8%), but raised again in 9-13 years to 59.2% in those who received the vaccine (20). Also in the study done in Iran by Hamkar et al., in 2003, the high percentages of low immune response (61.5%) and the low percentage of high immune response (37.6%) were found in the age 5 to 6-year-old age group. The ratio of low immune response in children age 6-10 decrease.

(9)

slightly to reach 48% while the high avidity response increase slightly to reach 51.2% (21).

A study in Singapore in 2018, which included 1,200 children and adolescents aged between 1–

17 years, showed seropositivity increased in age 1–6 years significantly from 91.0% to 96.8% in adolescents aged 13–17 years (22).

According to sex, the result showed vaccinated female with number 79 while a number of a vaccinated male was 101, the percentage of the female with a low immune response (19.0%) slightly higher than the male with 17.8%, while male show slightly higher percentage with 25.7% in high immune response with no significant difference.

In a study performed in Germany in 2012 in children for seroprevalence MMR-Antibody in children and adolescents aged from 0–17 years the difference non-significant in children but significant differences between male and female the difference was high in adolescents (23). In another study performed in Luxembourg from 2000–2001 to determine the antibody status against vaccine-preventable infections of the Luxembourg population showed no significant difference between genders in children and adolescents from samples collected randomly from primary and secondary schools. (24). In 2004 in Jeddah, Saudi Arabia in a study performed on 527 children (285 males and 242 females) aged between 4-14 years, the children aged between 4-6 years’ male was with significantly higher rubella seropositivity than female while children aged 7-11 years show no significant difference in seropositivity (25). Pankratz et al. in 2010 show a significant difference in the level of IgG antibody, in a study performed in 738 healthy young adult and children aged between 11-19 years (26). In 2005 study was performed in turkey to determine the seroprevalence of rubella in children (n=331) aged between 0 and 59 months show no significant difference between genders in seropositivity (27).

SNP/haplotype in cytokine and cytokine receptor genes and their association with rubella vaccine immune response in healthy 738 children aged 11–19 years (34).

The current study showed the number of children who had TNF-α homozygous wild type (GG) is 163, the number of children who had TNF-α homozygous mutant (TT or AA) was 9 and the number of children who had TNF-α heterozygous mutant (AG or TG) was 8. The homozygous and heterozygous mutant has a higher percentage with the low immune response with 22.2% and 25%respectively.

Also, this study showed significant statistical difference (p<0.05) between wild allele and mutant allele 2 (M2), the percentage of rubella IgG immune response was higher in M2in low and moderate immune response with 33.33%, 61.11% respectively than in wild allele which was 18.02% in low immune response and 57.36%. in the moderate immune response. While wild allele has a higher percentage in high immune response with 24.62% than in M2 with 5.56%.

This agrees with Dhiman et al. in 2010 who showed TNF-α gene SNP haplotype GTGCGGGGC, GAGAAGGGA, and GTGAAGGGA were associated with low rubella IgG levels. Also, they showed that specific genetic polymorphisms in IL12B and TNFRSF1B genes seem to be involved in the variations in rubella vaccine immune responses either directly or indirectly by controlling the action of other cytokines, such as IL-6 (34).

(10)

Ovsyannikova et al in 2009 showed an indirect effect of HLA alleles on rubella vaccine immune response through its effect on specific rubella T cell cytokine responses after rubella vaccine.

The HLA alleles effect on TNF-α either increasing or decreasing its level led to an effect on the immune response.

Alleles of HLA-A *0301 loci and *1101 loci appeared to be associated with a lower level of TNF-α cytokine response and led to the low immune response of rubella vaccine (35)

The result also showed heterozygous with a high percentage of high immune response with 37.5% as compared with homozygous mutant which was lower than.

References:

1. Cooper LZ. The history and medical consequences of rubella:clinical infectious diseases.1985. (Supplement_1) S2-10.

2. Hawker J, Begg N, Reintjes R,Ekdahl K, Edeghere O, Van Steenbergen JE.

Communicable Disease Control and Health Protection Handbook, 4th ed.; Wiley Blackwell: Oxford, UK, 2019; pp. 205–207.

3. Hobman T, Chanter J. Rubella virus. In: Knipe DM, Howley PM. Fields virology. 5th ed. Philadelphia: Wolters Kluwer; 2007. Pp. 1069–100.

4. Drutz JE, Duryea TK, Edwards MS, Torchia MM (Eds). Measles, mumps, and rubella immunization in infants, children, and adolescents(internet).UpToDate .2020(Dec8) Available from https://www.uptodate.com/contents/measles-mumps-and-rubella- immunization-in-infants-children-and-adolescents

5. World Health Organization. Global measles and rubella strategic plan 2012 -2020

(INTERNET).WHO Available

fromhttps://apps.who.int/iris/rest/bitstreams/53400/retrieve

6. Kimberlin D, Brady MT, Jackson MA, Long SS, editors. Red Book: Report of the Committee on Infectious Diseases. 31st ed. Itasca: American Academy of Pediatrics;

2018: 705-11

7. Riley L,Hirsch MS , Lockwood CJ , Bloom A , Eds. Rubella in pregnancy

(internet).uptodate 2019 (Oct24). Available from

https://www.uptodate.com/contents/rubella-in-pregnancy

8. Vesikari T, Becker T, Gajdos V, Fiquet A, Thomas S, Richard P, Baudin M.

Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad®)in infants from 9 months of age. Vaccine.

2012 Apr 26;30(20):3082-9.

(11)

9. Reef SE, Plotkin SA. Rubella vaccine. In: Plotkin SA, Orenstein W, Offit PA, editors. Vaccines. 6th ed. Elsevier; 2012. p. 688

10. Gillam S. The Jeanne Manery Fisher Memorial Lecture 1994. Molecular biology of rubella virus structural proteins. Biochem Cell Biol. 1994 Sep 1;72(9-10):349–56.

11. Reef SE, Plotkin SA. Rubella. In: Remington JS, Klein JO, Wilson CB, Nizet V, Maldonado YA, eds. Infectious Diseases of the Fetus and Newborn Infant. 8th ed.

Philadelphia: Elsevier; 2015. p. 894-932.

12. Cooper LZ. The burden of congenital rubella syndrome. In: de Quadros CA, editor.

Vaccines: preventing disease & protecting health. Washington: Pan American Health Organization; 2004. Pp. 53–64

13. Kennedy RB, Ovsyannikova IG, Haralambieva IH. Lambert ND, Pankratz VS, Poland GA. Genome-wide SNP associations with rubella-specific cytokine responses in measles- mumps-rubella vaccine recipients. Immunogenetics 2014 Aug;66(7):493-9.

14. Croft M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 2009; 9:271–285.

15. Jones SA. Directing transition from innate to acquired immunity: defining a role for IL-6.

J Immunol 2005; 175:3463–3468.

16. Bartee E, Mohamed MR, McFadden G. Tumor necrosis factor and interferon: cytokines in harmony. CurrOpin Microbial 2008; 11:378–383.

17. Clark IA. How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Rev. 2007 Jun–Aug; 18(3–4):335–343.

18. Pukhalsky AL, Shmarina GV, Bliacher MS, Fedorova IM, Toptygina AP, Fisenko JJ, Alioshkin VA. Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination. Mediators Inflamm 2003; 12:203–207.

19. Center for disease control and prevention. MMR Vaccination | What You Should Know | Measles, Mumps, Rubella | [Internet]. CDC. 2021 (4 February 2021]. Available from:

https://www.cdc.gov/vaccines/vpd/mmr/public/index.html

20. J Hasony H, Nazar Al-Musawi W. Seroprevalence to rubella virus post MMR vaccination in Basrah, southern Iraq. The Medical Journal of Basrah University. 2007 Dec 28;25(2):17-22.

(12)

21. 21 Hamkar R, Jalilvand S, Mokhtari-Azad T, Jelyani KN, NateghR.. Evaluation of immunity against rubella in Iranian after mass campaign for measles-rubella vaccination on December 2003. Am J Infect Control. 2006 Nov;34(9):588-92. doi:

10.1016/j.ajic.2005.11.005.

22. Ng Y, Chua LA, Cui L, Ang LW, Tee NW, Lin RT, Ma S, Lee VJ. Seroprevalence of vaccine-preventable diseases among children and adolescents in Singapore: Results from the National Paediatric Seroprevalence Survey 2018. Int J Infect Dis. 2020 Mar; 92:234- 240.

23. Poethko-Müller C, Mankertz A. Seroprevalence of measles-, mumps- and rubella-specific IgG antibodies in German children and adolescents and predictors for seronegativity.

PLoS One. 2012;7(8): e42867.

24. Mossong J, Putz L, Schneider F. Seroprevalence of measles, mumps and rubella antibodies in Luxembourg: results from a national cross-sectional study. Epidemiol Infect. 2004 Jan;132(1):11-18.

25. Jaber SM. A serological survey of measles, mumps and rubella immunity among school aged children in Western Saudi Arabia. Saudi Medical Journal. 2006 Jan;27(1):63-69.

26. Pankratz VS, Vierkant RA, O'Byrne MM, Ovsyannikova IG, Poland GA.Associations between SNPs in candidate immune-relevant genes and

27. rubella antibody levels: a multigenic assessment. BMC Immunol. 2010 Oct 5; 11:48. doi:

10.1186/1471-2172-11-48.

28. Aytac NE, Yucel AB, Yapicioglu HA, Kibar Fİ, Karaomerlioglu O, Akbaba MU. Rubella seroprevalence in children in Dogankent, a rural area of Adana province in Turkey, January-February 2005. Euro Surveill. 2009 Dec 17;14(50)

29. Chabalgoity JA, Baz A, Rial A, Grille S. The relevance of cytokines for development of protective immunity and rational design of vaccines. Cytokine Growth Factor Rev 2007;

18:195–207.

30. Keen LJ. The extent and analysis of cytokine and cytokine receptor gene polymorphism.

Transpl Immunol 2002; 10:143–146.

31. Hill AV. The genomics and genetics of human infectious disease susceptibility. Annual review of genomics and human genetics. 2001 Sep;2(1):373-400.

32. Skevaki C, Pararas M, Kostelidou K, Tsakris A, Routsias JG. Single nucleotide polymorphisms of T oll‐like receptors and susceptibility to infectious diseases. Clinical &

Experimental Immunology. 2015 May;180(2):165-177

33. Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008;214(2):149–60

34. Kwiatkowski D, Sambou I, Twumasi P, Greenwood BM, Hill AV, Manogue KR, Cerami A, Castracane J, Brewster DR. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990;336(8725):1201–1204.

35. Dhiman N, Haralambieva IH, Kennedy RB, Vierkant RA, O’Byrne MM, Ovsyannikova IG, Jacobson RM, Poland GA.SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine. Immunogenetics. 2010;62(4):197-210.

36. Ovsyannikova IG, Ryan JE, Vierkant RA, O’Byrne MM, Pankratz VS, Jacobson RM, Poland GA. Influence of host genetic variation on rubella-specific T cell cytokine responses following rubella vaccination. Vaccine. 2009 May 26;27(25-26):3359-3366.

(13)

37. Ovsyannikova IG, Salk HM, Larrabee BR, Pankratz VS, Poland GA. Single nucleotide polymorphisms/haplotypes associated with multiple rubella-specific immune response outcomes post-MMR immunization in healthy children.

Referințe

DOCUMENTE SIMILARE

The averaging theory is one of the most powerfrrl tools in approaching problems governed by differential equations, The goal of this note is to present a theoretical

Another objective was to investigate the effect of anodization temperature on the current – time response, current density of anodization, AAO film thickness, activation

According to our previous investigations it seems that tolerance, whether regarded as a political practice or a philosophical or moral principle, is a strategy (or tactics) of one

The number of vacancies for the doctoral field of Medicine, Dental Medicine and Pharmacy for the academic year 2022/2023, financed from the state budget, are distributed to

Genotyping was performed utilizing single stranded polymorphism-polymerase chain response (SSP-PCR).Resultshis study revealed that IFNγ+874 AT genotype was

However, few studies on mumps was conducted in Iraq during the last few years, a study in 2017 showed that form a total of 3176 participants 58.6% was confirmed to be

Objectives: This study sought to assess the effect of local injection of platelet-rich plasma (PRP) on level of interleukin 1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)

The product may be natural or synthetic.The peptide vaccines are considered as an alternative to classical vaccines that try to address the issue of possible