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Verma, Deepti
Publications (10 of 21) Show all publications
Das, J., Verma, D., Gustafsson, M. & Lerm, M. (2019). Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naive subjects. Epigenetics, 14(6), 589-601
Open this publication in new window or tab >>Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naive subjects
2019 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, no 6, p. 589-601Article in journal (Refereed) Published
Abstract [en]

The protection against tuberculosis induced by the Bacille Calmette Guerin (BCG) vaccine is unpredictable. In our previous study, altered DNA methylation pattern in peripheral blood mononuclear cells (PBMCs) in response to BCG was observed in a subgroup of individuals, whose macrophages killed mycobacteria effectively (responders). These macrophages also showed production of Interleukin-1 beta (IL-1 beta) in response to mycobacterial stimuli before vaccination. Here, we hypothesized that the propensity to respond to the BCG vaccine is reflected in the DNA methylome. We mapped the differentially methylated genes (DMGs) in PBMCs isolated from responders/non-responders at the time point before vaccination aiming to identify possible predictors of BCG responsiveness. We identified 43 DMGs and subsequent bioinformatic analyses showed that these were enriched for actin-modulating pathways, predicting differences in phagocytosis. This could be validated by experiments showing that phagocytosis of mycobacteria, which is an event preceding mycobacteria-induced IL-1 beta production, was strongly correlated with the DMG pattern.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC, 2019
Keywords
DNA methylation; BCG-vaccination; phagocytosis; actin regulation; Mycobacterium tuberculosis; Tuberculosis
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-158857 (URN)10.1080/15592294.2019.1603963 (DOI)000471388000001 ()31010371 (PubMedID)
Note

Funding Agencies|Hjart-Lungfonden [20150709]; Vetenskapsradet [2012-3349]

Available from: 2019-07-15 Created: 2019-07-15 Last updated: 2019-07-25
Sigurdardottir, G., Ekman, A.-K., Verma, D. & Enerbäck, C. (2018). Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.. Dermatology, 234(5-6), 173-179
Open this publication in new window or tab >>Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.
2018 (English)In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 234, no 5-6, p. 173-179Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment.

OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis.

METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response.

RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction.

CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.

Place, publisher, year, edition, pages
Basel: S. Karger, 2018
Keywords
Cardiovascular risk, Psoriasis, Skin, UVB
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-151989 (URN)10.1159/000491819 (DOI)000451050100003 ()30176661 (PubMedID)
Funder
Ingrid Asp Psoriasis Research Center
Note

This research was funded by the Ingrid Asp Foundation, the Welander Foundation, the Swedish Psoriasis Association, and the Medical Research Council.

Available from: 2018-10-12 Created: 2018-10-12 Last updated: 2019-05-01
Noren, E., Verma, D., Söderkvist, P., Weisselberg, T., Söderman, J., Lotfi, K. & Almer, S. (2016). Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation. Annals of Transplantation, 21, 56-67
Open this publication in new window or tab >>Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation
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2016 (English)In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 21, p. 56-67Article in journal (Refereed) Published
Abstract [en]

Background: Non-HLA genes may contribute to the prognosis after hematopoietic stem cell transplantation. We investigated associations between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation. Material/Methods: Single nucleotide polymorphisms in selected regions were determined and analyzed for putative associations with overall mortality and acute graft-versus-host disease. Significant associations were further explored by logistic regression, controlling for additional variables. Results: A significant association was identified between overall mortality among recipients and a nonsynonymous coding variant of MORC4 (rs6622126) in the recipient genetic makeup (P=0.029). Since MORC4 is located on the X-chromosome, the results were also analyzed separately for males and females. The association between overall mortality for recipients and the risk allele (rs6622126; A) was confirmed for males with respect to genetic makeup of recipients (P=0.012), donor genetic makeup (P=0.004), and the combined allele composition of the donor and recipient (P=0.001). A significant association was also identified between overall mortality and the recipient risk allele of CD14 (rs2569190; P=0.031), TLR4 (rs4986790; P=0.043), and NOD2 (carriage of at least 1 mutant allele of rs2066844, rs2066845, or rs2066847; P=0.048). Among the investigated genes, only the CD14 (rs2569190) recipient risk allele was significantly associated with acute graft-versus-host disease (P=0.023). Logistic regression models confirmed these findings, except for NOD2, and also identified a significant contribution by age at stem cell transplantation (MORC4, CD14, TLR4), diagnosis (CD14, TLR4), and prophylaxis (MORC4). Conclusions: Genetic variation in MORC4, CD14, and TLR4 may affect the outcome of allogeneic stem cell transplantation.

Place, publisher, year, edition, pages
Warsaw, Poland: International Scientific Literature, 2016
Keywords
Association Studies; Genetic Predisposition to Disease; Graft vs. Host Disease; Polymorphism, Single Nucleotide; Transplantation, Homologous
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126266 (URN)000371110000001 ()
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-05-03Bibliographically approved
Ekman, A.-K., Verma, D., Fredrikson, M., Bivik, C. & Enerbäck, C. (2014). Genetic variations of NLRP1: susceptibility in psoriasis. British Journal of Dermatology, 171(6), 1517-1520
Open this publication in new window or tab >>Genetic variations of NLRP1: susceptibility in psoriasis
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2014 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1517-1520Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.

OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.

MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.

RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.

CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112730 (URN)10.1111/bjd.13178 (DOI)000347236100197 ()24909542 (PubMedID)
Note

The study was funded by the Ingrid Asp foundation, the Welander Foundation and the Swedish Psoriasis Association.

Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-01-11Bibliographically approved
Eklund, D., Welin, A., Andersson, H., Verma, D., Söderkvist, P., Stendahl, O., . . . Lerm, M. (2014). Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis. The Journal of infectious diseases, 209(5), 749-753
Open this publication in new window or tab >>Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis
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2014 (English)In: The Journal of infectious diseases, ISSN 1537-6613, Vol. 209, no 5, p. 749-753Article in journal (Refereed) Published
Abstract [en]

Activation of the NLRP3 inflammasome and subsequent generation of IL-1β is initiated in macrophages upon recognition of several stimuli. In the present work, we show that gain-of-function gene variants of inflammasome components known to predispose individuals to inflammatory disorders have a host-protective role during infection with Mycobacterium tuberculosis. By isolation of macrophages from patients and healthy blood donors with genetic variants in NLRP3 and CARD8 and subsequently infecting the cells by virulent M. tuberculosis, we show that these gene variants, combined, are associated with increased control of bacterial growth in human macrophages.

Place, publisher, year, edition, pages
University of Chicago Press / Oxford University Press (OUP), 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-100889 (URN)10.1093/infdis/jit572 (DOI)000331873700016 ()24158955 (PubMedID)
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2015-04-10Bibliographically approved
Kastbom, A., Klingberg, E., Verma, D., Carlsten, H., Forsblad-dElia, H., Wesamaa, J., . . . Söderkvist, P. (2013). Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis. Scandinavian Journal of Rheumatology, 42(6), 465-468
Open this publication in new window or tab >>Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis
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2013 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, no 6, p. 465-468Article in journal (Refereed) Published
Abstract [en]

Objectives: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is important for interleukin-1beta (IL-1 beta) processing as part of an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is an inhibitor of nuclear factor kappa B (NF-kappa B) and possibly also a part of the NLRP3 inflammasome. The objective of this study was to evaluate one single nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing spondylitis (AS) susceptibility and disease phenotype. less thanbrgreater than less thanbrgreater thanMethod: We recruited 492 AS patients from Southern Sweden fulfilling the modified New York criteria for AS, and assessed phenotypic characteristics from medical records and questionnaires. Patients with psoriasis or clinically overt inflammatory bowel disease (IBD) were excluded, as were patients without human leucocyte antigen B27 (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and the results compared at genotype and allele levels to those of 793 population-based controls. In a subgroup of the patients (n = 169), faecal calprotectin was assessed as a marker of subclinical intestinal inflammation. less thanbrgreater than less thanbrgreater thanResults: The minor allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54-0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02), but was not associated with levels of faecal calprotectin. There was no association regarding NLRP3 SNPs and AS susceptibility, and none of the investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti-TNF) therapy, or peripheral joint involvement. less thanbrgreater than less thanbrgreater thanConclusion: In a Swedish population, the minor allele of CARD8-C10X is associated with a decreased risk of AS, but not with levels of faecal calprotectin or disease phenotype.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102509 (URN)10.3109/03009742.2013.779020 (DOI)000327259200007 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden (FORSS)|FORSS-88721|County Council of Ostergotland||

Available from: 2013-12-12 Created: 2013-12-12 Last updated: 2017-12-06
Bivik, C., Verma, D., Winge, M. C., Lieden, A., Bradley, M., Rosdahl, I. & Söderkvist, P. (2013). Letter: Genetic Variation in the Inflammasome and Atopic Dermatitis Susceptibility [Letter to the editor]. Journal of Investigative Dermatology, 133(10), 2486-2489
Open this publication in new window or tab >>Letter: Genetic Variation in the Inflammasome and Atopic Dermatitis Susceptibility
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2013 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 133, no 10, p. 2486-2489Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option A, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99395 (URN)10.1038/jid.2013.168 (DOI)000324899100028 ()
Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2017-12-06
Pihl, M., Verma, D., Fredrikson, M., Söderkvist, P., Ludvgisson, J. & Casas, R. (2013). Polymorphisms in NALP3 inflammasome components NLRP3 and CARD8 affect C-peptide secretion in type 1 diabetes.
Open this publication in new window or tab >>Polymorphisms in NALP3 inflammasome components NLRP3 and CARD8 affect C-peptide secretion in type 1 diabetes
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Interleukin-1β has long been known to have potential roles in type 1 diabetes (T1D) pathogenesis. Production of active Iinterleukin-1β is dependent on the action of a caspase activating protein complex called NALP3 inflammasome. The NALP3 inflammasome is composed of NALP3/Cryopyrin, ASC and CARD8. Polymorphisms in the NLRP3 and CARD8 genes have been linked to several autoinflammatory diseases. The NALP3 inflammasome is crucial for adjuvanticity of aluminium hydroxide, which is used as adjuvant in clinical trials of glutamic acid decarboxylase (GAD)-alum in T1D. Our aim was to investigate the effect of common polymorphisms of NLRP3 on T1D susceptibility as well as on GAD-alum treatment efficacy. The single nucleotide polymorphisms NLRP3 Q705K, CARD8 C10X and an SNP downstream of the NLRP3 gene, rs10733113, were genotyped using a Taqman genotyping assay. The A allele of CARD8 C10X was associated with a lower stimulated insulin secretion 3 months after diagnosis in males. Patients with at least one G allele at rs10733113 were more likely to produce auto-antibodies against two or more of the islet antigens GAD, Insulin or IA-2. None of the genotyped SNPs had any significant influence on efficacy of GAD-alum treatment, but individuals with at least one rs10733113 G allele treated with placebo had lower residual insulin secretion than those with the AA genotype at 9, 15 and 21 months after start of treatment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98248 (URN)
Available from: 2013-10-04 Created: 2013-10-04 Last updated: 2013-10-04Bibliographically approved
Blomgran, R., Brodin Patcha, V., Verma, D., Bergström, I., Söderkvist, P., Sjöwall, C., . . . Sarndahl, E. (2012). Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils. PLoS ONE, 7(3)
Open this publication in new window or tab >>Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3Article in journal (Refereed) Published
Abstract [en]

Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77736 (URN)10.1371/journal.pone.0031326 (DOI)000303017700010 ()
Note
Funding Agencies|Swedish Research Council||Heart-Lung Foundation||King Gustaf V Memorial Foundation||County Council of Ostergotland||Soderberg Foundation||Available from: 2012-05-29 Created: 2012-05-28 Last updated: 2017-12-07
Ungerbäck, J., Belenki, D., Jawad Ul-Hassan, A., Fredrikson, M., Fransén, K., Elander, N., . . . Söderkvist, P. (2012). Genetic variation and alterations of genes involved in NFκB/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer. Carcinogenesis, 33(11), 2126-2134
Open this publication in new window or tab >>Genetic variation and alterations of genes involved in NFκB/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer
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2012 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 33, no 11, p. 2126-2134Article in journal (Refereed) Published
Abstract [en]

Colorectal tumors are continuously exposed to an inflammatory environment, which together with mitogenic signals sustain several cancer hallmarks. Nuclear factor-kappa B (NFκB) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with increased risk of colorectal cancer (CRC) development, and/or a rapidly progressing disease. In this study, 348 CRC cases and 806 randomly selected healthy individuals from southeastern Sweden were examined with regard to seven polymorphisms in NFκB pathway-associated genes. Log-rank-tests and Cox proportional hazard regression analysis examined the association between the polymorphisms and CRC-specific survival, whereas chi-square tests and logistic regression analysis were used to test for associations between the polymorphisms and CRC susceptibility. Gene expression and loss of heterozygosity analyses of TNFAIP3 were carried out in a subset of tumors to assess its role as a tumor suppressor in CRC. Heterozygous and polymorphic TNFAIP3 (rs6920220), heterozygous NLRP3 (Q705K) and polymorphic NFκB -94 ATTG ins/del genotypes were found to be associated with poorer survival in patients diagnosed with invasive CRC (aHR = 5.2, 95% CI: 2.5-10.9, P < 0.001). TNFAIP3 mRNA levels were significantly decreased in tumors compared with adjacent non-neoplastic mucosa (P < 0.0001) and loss of heterozygosity of 6q23.3 (TNFAIP3) was detected in 17% of cases, whereas only 2.5% of the investigated specimens displayed TNFAIP3 gene mutations. We propose that TNFAIP3 (rs6920220), NLRP3 (Q705K) and NFκB -94 ATTG ins/del polymorphisms are associated with poor survival in patients with advanced CRC and may be used as prognostic markers. Experimental results indicate that TNFAIP3 may act as a tumor suppressor in CRC.

Place, publisher, year, edition, pages
Oxford University Press, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80806 (URN)10.1093/carcin/bgs256 (DOI)000310624400014 ()22843550 (PubMedID)
Note

funding agencies|Swedish Research Council|2010-55X-20451-04-3|

Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2017-12-07
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