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Dahle, Charlotte
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Publications (10 of 41) Show all publications
Theodorsson, E., Löwbeer, C., Ridefelt, P., Carlson, M., Dahle, C. & Simonsson, P. (2018). Digestionsorganens sjukdomar (10ed.). In: Laurells klinisk kemi i praktisk medicin: (pp. 465-516). Lund: Studentlitteratur AB
Open this publication in new window or tab >>Digestionsorganens sjukdomar
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2018 (Swedish)In: Laurells klinisk kemi i praktisk medicin, Lund: Studentlitteratur AB, 2018, 10, p. 465-516Chapter in book (Other academic)
Place, publisher, year, edition, pages
Lund: Studentlitteratur AB, 2018 Edition: 10
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-154593 (URN)9789144119748 (ISBN)
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-02-21
Oji, S., Nicolussi, E.-M., Kaufmann, N., Zeka, B., Schanda, K., Fujihara, K., . . . Bradl, M. (2016). Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord. PLoS ONE, 11(3), e0151244
Open this publication in new window or tab >>Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, p. e0151244-Article in journal (Refereed) Published
Abstract [en]

Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127436 (URN)10.1371/journal.pone.0151244 (DOI)000372582800051 ()26990978 (PubMedID)
Note

Funding Agencies|Austrian Science Fund [P25240-B24]; Austrian Ministry of Science, Research and Economy (BIGWIG-MS); Ministry of Education, Culture, Sports, Science and Technology of Japan; Alumni Association of Saitama Medical University

Available from: 2016-05-01 Created: 2016-04-26 Last updated: 2017-11-30
Wågström, P., Bengnér, M., Dahle, C., Nilsdotter-Augustinsson, Å., Neumark, T., Brudin, L. & Björkander, J. (2015). Does the frequency of respiratory tract infections help to identify humoral immunodeficiencies in a primary health-care cohort?. Scandinavian Journal of Infectious Diseases, 47(1), 13-19
Open this publication in new window or tab >>Does the frequency of respiratory tract infections help to identify humoral immunodeficiencies in a primary health-care cohort?
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2015 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 47, no 1, p. 13-19Article in journal (Refereed) Published
Abstract [en]

Background: Primary immune deficiency (PID) due to humoral defects is associated with recurrent respiratory tract infections (RTIs). Reliable clinical warning signs of PID would facilitate early diagnosis and thereby reduce long-term complications. The aim of the present study was to evaluate the accuracy of the warning sign, 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years,' for detecting PID among adults in a primary health-care setting. Methods: Fifty-three cases with 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years' were selected from a Swedish primary health-care registry of RTIs. In addition, 66 age- and sex-matched controls were selected having a maximum of one antibiotic-treated RTI during the period covered by the study. Levels of immunoglobulin (Ig) IgG, IgA, IgM, IgG subclasses, and IgG antibodies against Haemophilus influenzae and Streptococcus pneumoniae as well as the inflammatory markers, C-reactive protein, interleukin (IL)-6 and IL-8 were determined. Results: IgG subclass deficiencies (IgGsd) were found in 5/53 (9.4%) of the cases and in 7/66 (10.6%) controls. The most frequent deficiency was IgG3sd and this was found in three participants in the case group and seven in the control group. The mean level of IgG3 was lower in the control group (p = 0.02). The mean level of IL-8 was lower in the case group (p = 0.02). Conclusion: The results show that physicians working in primary health care cannot solely rely on the frequency of antibiotic-treated RTIs as a warning sign for the detection of common humoral immune deficiencies.

Place, publisher, year, edition, pages
Informa Healthcare, 2015
Keywords
Clinical warning sign; immunoglobulin deficiency; primary health care; respiratory tract infections
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112726 (URN)10.3109/00365548.2014.956330 (DOI)000350052400003 ()25378084 (PubMedID)
Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2017-12-05
Enocsson, H., Sjöwall, C., Wirestam, L., Dahle, C., Kastbom, A., Ronnelid, J., . . . Skogh, T. (2015). Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity. Journal of Rheumatology, 42(5), 817-825
Open this publication in new window or tab >>Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity
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2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 5, p. 817-825Article in journal (Refereed) Published
Abstract [en]

Objective. Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables. Methods. Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjogren syndrome (n = 54) served as controls. Results. CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fishers exact test revealed striking differences between methods regarding associations with certain disease phenotypes. Conclusion. CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2015
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; DOUBLE-STRANDED DNA; IMMUNOASSAY; AUTOANTIBODIES; INFLAMMATION; RHEUMATIC DISEASE
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118866 (URN)10.3899/jrheum.140677 (DOI)000353779400013 ()25684763 (PubMedID)
Note

Funding Agencies|Swedish Research Council [K2012-69X-14594-10-3, K2011-68X-20611-04-3]; Swedish Society for Medicine [SLS-331171]; Swedish Society Against Rheumatism [R-313701, R-307291]; Swedish Society for Medical Research; King Gustaf V 80-year Foundation [FAI2013-0066]; Professor Nanna Svartz foundation

Available from: 2015-06-08 Created: 2015-06-04 Last updated: 2018-11-07
Kang Lim, C., Dahle, C., Elvin, K., Andersson, B. A., Ronnelid, J., Melen, E., . . . Hammarstrom, L. (2015). Reversal of Immunoglobulin A Deficiency in Children. Journal of Clinical Immunology, 35(1), 87-91
Open this publication in new window or tab >>Reversal of Immunoglobulin A Deficiency in Children
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2015 (English)In: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 35, no 1, p. 87-91Article in journal (Refereed) Published
Abstract [en]

Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keywords
IgA deficiency; reversal; diagnostic definition
National Category
Immunology in the medical area Pediatrics
Identifiers
urn:nbn:se:liu:diva-115004 (URN)10.1007/s10875-014-0112-6 (DOI)000348805600013 ()25370723 (PubMedID)
Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2018-01-11
Wickström, A., Dahle, C., Vrethem, M. & Svenningsson, A. (2014). Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial. Multiple Sclerosis, 20(8), 1095-1101
Open this publication in new window or tab >>Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial
2014 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 8, p. 1095-1101Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

OBJECTIVES:

The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

METHODS:

This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial.

RESULTS:

MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizumab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

CONCLUSIONS:

This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

Place, publisher, year, edition, pages
Sage Publications, 2014
Keywords
Multiple sclerosis; work ability; fatigue; motor fatigue; walking distance; biological drugs; natalizumab
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109239 (URN)10.1177/1352458513517590 (DOI)000338819400012 ()24378984 (PubMedID)
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
Edström, M., Dahle, C., Vrethem, M., Gustafsson, M., Benson, M., Jenmalm, M. & Ernerudh, J. (2014). Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines.
Open this publication in new window or tab >>Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND Regulatory T cells (Treg) are critical for immune regulation and homeostasis. In multiple sclerosis (MS), the function of these cells has been shown to be impaired, although the underlying mechanism has yet to be shown. In the current study, we aimed to characterize and assess the phenotypical, functional and transcriptional characteristics of memory and naïve Treg in MS patients and controls.

MATERIAL AND METHODS 27 patients with relapsing-remitting disease were included, along with 29 healthy controls. Flow cytometry was used for detailed phenotyping of Treg subpopulations CD4+CD45RA+/- and CD4dimCD25++ and their expression of FOXP3, CD39 and HELIOS. CFSE (proliferation marker) and CD69 (activation marker) were used to investigate the functional capacity of Treg. A microarray was employed for genome-wide transcriptional characterization of isolated Treg.

RESULTS CD4+CD45RA–CD25++ activated Treg displayed a higher expression of FOXP3 and CD39 than resting CD4+CD45RA+CD25+ Treg, while no significant phenotypical differences were observed in Treg subpopulations between patients and controls. However, a lower anti-proliferative capacity was observed in activated Treg of MS patients compared with those of controls (p<0.05), while suppression of activation was similar to controls. Gene set enrichment analysis (GSEA) of microarray data revealed enrichment for the GO gene set ‘chemokine receptor binding’ in MS Treg.

CONCLUSION Although numerical phenotypical assessment of resting and activated Tregs did not reveal any significant difference between patients and controls, functional co-culturing experiments showed an impaired function in activated Treg of MS patients. Furthermore, GSEA revealed immune-related gene sets overexpressed in Treg of MS patients, possibly containing clues to the functional impairment. In particular over-activity in chemokine signalling in Treg would be of interest for further investigation.

Keywords
EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-108908 (URN)
Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2018-01-11Bibliographically approved
Wang, N., Truedsson, L., Elvin, K., Andersson, B. A., Ronnelid, J., Mincheva-Nilsson, L., . . . Dahle, C. (2014). Serological Assessment for Celiac Disease in IgA Deficient Adults. PLoS ONE, 9(4), 0093180
Open this publication in new window or tab >>Serological Assessment for Celiac Disease in IgA Deficient Adults
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. 0093180-Article in journal (Refereed) Published
Abstract [en]

Purpose: Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet. Methods: Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-even IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected. Results: Out of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti- DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not. Conclusions: IgG anti- tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.

Place, publisher, year, edition, pages
Public Library of Science, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106678 (URN)10.1371/journal.pone.0093180 (DOI)000334159800025 ()
Available from: 2014-05-21 Created: 2014-05-19 Last updated: 2017-12-05
Mellergård, J., Edström, M., Jenmalm, M., Dahle, C., Vrethem, M. & Ernerudh, J. (2013). An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients. PLoS ONE, 8(12), Article ID e81685.
Open this publication in new window or tab >>An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81685Article in journal (Refereed) Published
Abstract [en]

Background

Changes in the peripheral blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.

Objectives

To assess changes in circulating lymphocyte subpopulation compositions and T-cell responses during natalizumab treatment.

Material and methods

A broad panel of markers for blood lymphocyte populations, including states of activation and co-stimulation as well as T-cell responses to recall antigens and mitogens, was assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after one-year natalizumab treatment.

Results

Absolute numbers of all major populations of lymphocytes increased after treatment, most markedly for NK- and B-cells. The fraction of both memory and presumed regulatory B-cell subsets increased, as did CD3-CD56dim cytotoxic NK-cells, whereas CD3-CD56bright regulatory NK-cells decreased. Treatment was also associated with a restored T-cell responsiveness to recall antigens and mitogens.

Conclusions

Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK- and B-cells. This supports reduction of lymphocyte extravasation as a main mode of action, although the differential composition of lymphocyte subpopulations suggests cell-signalling effects may also be operative. The systemic increase in T-cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses become correspondingly decreased.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, 2013
Keywords
Multiple sclerosis, natalizumab, flow cytometry, T-cells, NK-cells, B-cells, lymphocyte proliferation
National Category
Neurology Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-84268 (URN)10.1371/journal.pone.0081685 (DOI)000327944500088 ()24312575 (PubMedID)2-s2.0-84891420120 (Scopus ID)
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2018-01-12Bibliographically approved
Vrethem, M., Lindh, J., Tondel, M., Persson, B. & Dahle, C. (2013). IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy. Acta Neurologica Scandinavica, 127(2), 109-115
Open this publication in new window or tab >>IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy
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2013 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 109-115Article in journal (Refereed) Published
Abstract [en]

Objectives To study the prevalence of antibodies of IgA class against tissue transglutaminase (tTG), endomysium (EMA) and gliadin (AGA) in patients with chronic idiopathic axonal polyneuropathy (CIAP) and to characterize the patients clinically and neurophysiologically. Methods Of 182 patients, 126 patients agreed to blood sampling. Sera were analysed by ELISAs detecting anti-tTG and AGA, whereas EMA was analysed by indirect immunofluorescence (IF) microscopy. Gastrointestinal symptoms were assessed by data from medical records and patient interviews. Results Nine of 126 patients (7%) were seropositive in at least one test (five with positive anti-tTG and/or EMA and four with positive AGA only). One patient with elevated levels of all specificities had laboratory signs of malabsorption and gastrointestinal complaints with abdominal pain and diarrhoea. Conclusions Elevated levels of IgA-AGA were slightly more frequent in patients with CIAP (4%) compared to 2.5% in 1866 healthy blood donors. Highly specific serological markers indicative of coeliac disease (CD) (anti-tTG and EMA) were somewhat more common in our patients with CIAP (4%) than expected from normal reference values and from studies of the prevalence of CD in the general population. Even though these findings may indicate a relationship, the aetiological importance is unclear.

Place, publisher, year, edition, pages
John Wiley and Sons, 2013
Keywords
neuropathy, idiopathic, gluten sensitivity, coeliac disease, anti-tissue transglutaminase, anti-gliadin, anti-endomysium
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-89742 (URN)10.1111/j.1600-0404.2012.01687.x (DOI)000313886700007 ()
Note

Funding Agencies|Swedish Council for Work Life and Social Research||Medical Research Council of Southeast Sweden (FORSS)||

Available from: 2013-03-07 Created: 2013-03-05 Last updated: 2017-12-06
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