Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto, a strict gluten-free diet is the only effective treatment and is necessary for good control of the disease. Serological tests in current use have very high specificity and sensitivity for diagnostics, but in follow-up they have some limitations. Their levels do not accurately reflect mucosal healing, and they are unable to detect minimal transgressions in the diet. This problem is significant in patients with IgA deficiency, and there exist no robust follow-up tools for monitoring these patients' adherence to treatment. For their follow-up, we currently use IgG-based tests, and these antibodies persist for a long time even when a patient has stopped consuming gluten. More accurate and specific biomarkers are definitely needed. Adherence to a gluten-free diet is essential not only for intestinal mucosa healing and alleviation of symptoms but also for preventing complications associated with celiac disease. Here, we summarize current evidence regarding noninvasive biomarkers potentially useful for follow-up not only of patients with IgA deficiency but for all patients with celiac disease. We describe several very promising biomarkers with potential to be part of clinical practice in the near future.

• MeSH
• Diet, Gluten-Free MeSH
• Biomarkers MeSH
• Celiac Disease * MeSH
• IgA Deficiency * MeSH
• Glutens MeSH
• Immunoglobulin A MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• MeSH
• Agammaglobulinemia diagnosis   drug therapy   MeSH
• Common Variable Immunodeficiency diagnosis   immunology   therapy   MeSH
• IgA Deficiency MeSH
• Hyper-IgM Immunodeficiency Syndrome diagnosis   therapy   MeSH
• Immunologic Tests methods   MeSH
• Humans MeSH
• Neonatal Screening MeSH
• Primary Immunodeficiency Diseases diagnosis   therapy   MeSH
• Antibodies analysis   blood   MeSH
• Immunologic Deficiency Syndromes * diagnosis   therapy   MeSH
• Vaccination methods   MeSH
• Check Tag
• Humans MeSH

• Keywords
• Goodův syndrom,
• MeSH
• Common Variable Immunodeficiency immunology   complications   MeSH
• IgA Deficiency immunology   complications   MeSH
• Adult * MeSH
• Humans MeSH
• Delayed Diagnosis MeSH
• Primary Immunodeficiency Diseases * diagnosis   therapy   MeSH
• Check Tag
• Adult * MeSH
• Humans MeSH
• Publication type
• Review MeSH

Selektivní deficit imunoglobulinu A je nejčastější primární imunodeficiencí, se kterou se může setkat klinický alergolog-imunolog. Tato kazuistika popisuje případ dvou sourozenců se selektivním deficitem imunoglobulinu A s rozdílnou klinickou manifestací. Zejména je popisováno významné neurologické postižení s přítomností anti-Hu protilátek a zvažovanou paraneoplastickou etiologií u jednoho z nich.

Selective immunoglobulin A deficiency is the most common primary immunodeficiency that a clinical allergist-immunologist may encounter. This case report describes the case of 2 sib-lings with selective immunoglobulin A deficiency with different clinical manifestations. In particular, a significant neurological impairment with the presence of anti-Hu antibodies and considered paraneoplastic etiology in one of them is described.

• MeSH
• IgA Deficiency * diagnosis   epidemiology   therapy   MeSH
• Hydrocortisone administration & dosage   therapeutic use   MeSH
• Immunoglobulin A MeSH
• Immunoglobulins, Intravenous administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Young Adult MeSH
• Siblings MeSH
• Immunologic Deficiency Syndromes MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Pro vysokou prevalenci je celiakie jedním z nejdůležitějších onemocnění trávicího ústrojí. Pacientů je přibližně 1 % v populaci, a proto je vyhledávání tohoto onemocnění nezbytné. Prvním krokem v diagnostice celiakie je vyšetření protilátek proti tkáňové transglutamináze ve třídě A imunoglobulinů (anti‑TG‑IgA) a vyloučení deficitu IgA stanovením jeho celkové hodnoty. Tato kombinace dvou vyšetření je nejpřesnějším a nejrentabilnějším úvodním vyšetřením. Během prvního vyšetření není potřeba stanovovat protilátky proti endomysiu ve třídě IgA (EMA‑IgA) a protilátky proti deamidovanému gliadinu ve třídě G imunoglobulinů (anti‑DGP- IgG). Pokud má dítě dvakrát, tj. i ve druhém vzorku krve 10× vyšší hodnoty anti‑TG‑IgA a současně je také pozitivní EMA -IgA, je možno stanovit diagnózu celiakie bez následné biopsie. Děti, u kterých byla nalezena hodnota anti‑TG‑IgA nižší než 10násobek normální hodnoty, mají podstoupit střevní biopsii ke snížení rizika falešně pozitivní diagnózy. HLA vyšetření a přítomnost symptomů nejsou potřeba ke stanovení diagnózy celiakie bez biopsie.

For high prevalence celiac disease (CD) is one of the most important diseases of the digestive tract. Patients are approximately 1% in the population and therefore a search for this disease is necessary. The first step in the diagnosis of CD is to test antibodies to tissue transglutaminase in class A immunoglobulins (anti-TG-IgA) and to eliminate IgA deficiency by determining its total value. This combination of total IgA and anti-TG- IgA is the most accurate and cost-effective initial testing. At this time, there is no need to test antibodies to endomysium in class IgA (EMA-IgA) and antibodies to deamided gliadin in class G immunoglobulins (anti-DGP-IgG). If the child was twice found high values of the anti-TG-IgA >10 times the upper normal limit (ULN), i.e. even in the second blood sample and at the same time was also positive EMA-IgA, it is possible to make the diagnosis of CD without biopsy. Children who have been found to have an anti-TG-IgA value <10 times ULN should undergo an intestinal biopsy to reduce the risk of false positive diagnosis. HLA testing and presence of symptoms are not needed for a sérology based diagnosis without biopsy.

• MeSH
• Autoantibodies blood   MeSH
• Biopsy standards   MeSH
• Celiac Disease * diagnosis   genetics   immunology   MeSH
• IgA Deficiency MeSH
• Child MeSH
• Duodenum pathology   MeSH
• Gliadin immunology   MeSH
• Glutens adverse effects   MeSH
• HLA-DQ Antigens genetics   MeSH
• Humans MeSH
• Practice Guidelines as Topic MeSH
• Transglutaminases immunology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH

Screening for celiac disease (CD) dramatically improved when techniques able to measure blood autoantibodies against tissue transglutaminase 2 (TTG) were developed. Although typically increased in CD, these antibodies are not pathognomonic since they are also detected in several other autoimmune processes. IgA deficiency among celiac patients is more frequent than in general population (up to 25% vs 1-3%). This led to develop kits able to measure IgG-TTG, which until today represent a helpful diagnostic tool during diagnosis of CD in IgA deficient individuals. Today, commercial kits measuring IgG- TTG (and other) antibodies are widely available, are frequently used and create confusion in diagnosing CD in IgA-sufficient individuals. This is attributed to the fact that sensitivity and specificity of IgG-TTG is lower when applied to IgA-sufficient persons, and also because IgG-TTG is detected in several autoimmune disorders, with variable frequency and isotypes depending on the condition. Evidence analyzed indicate that to date available data: i) is insufficient to understand the difference of classes and subclasses detected in CD and other autoimmune conditions; ii) does not support the use of IgG-TTG for diagnosing CD in IgA-sufficient individuals and therefore iii) IgG should not be used in the routine diagnostic process of CD.

• MeSH
• Autoantibodies blood   MeSH
• Celiac Disease * diagnosis   physiopathology   prevention & control   MeSH
• IgA Deficiency * complications   MeSH
• Immunoglobulin A blood   MeSH
• Immunoglobulin G blood   MeSH
• Humans MeSH
• Predictive Value of Tests MeSH
• Serologic Tests MeSH
• Transglutaminases immunology   blood   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Common Variable Immunodeficiency * diagnosis   genetics   MeSH
• IgA Deficiency genetics   MeSH
• Humans MeSH
• Immunologic Deficiency Syndromes * diagnosis   etiology   genetics   MeSH
• Research MeSH
• Check Tag
• Humans MeSH

Celiac disease has been associated with selective IgA immunoglobulin deficiency. A celiac disease cohort of 234 biopsy-defined adults (including 73 males and 161 females) from a 30-year period from 1982 to 2011 was reviewed. A total of 7 with selective IgA immunoglobulin deficiency were noted, or about 3%. All were female with an initial positive biopsy for untreated celiac disease. All had characteristic small intestinal biopsy features of severe histopathological adult disease and additional biopsies demonstrated a histopathological response after 1 to 10 years on a strict gluten-free diet. For 6 of the 7, diagnosed at ages 24 to 40 years, follow-up biopsies were either normal or showed only minimal epithelial lymphocytosis. In addition, a 71 year old female had a limited but definite histopathological response to a gluten-free diet. Although there was no microscopic evidence for a malignant lymphoma, added biopsies for molecular gene re-arrangement studies revealed a monoclonal lymphocyte population suggesting an occult or cryptic T-cell lymphoma. Gastric and colonic biopsies showed no abnormalities or evidence of epithelial lymphocytosis. In all of those tested, IgA antibodies to tissue transglutaminase were detected, occasionally even at high levels. In these, a gluten-free diet serological response was detected. Together, these findings demonstrate a heterogeneous serological response to a gluten-free diet in adult celiac disease accompanied by selective immunoglobulin deficiency

• MeSH
• Biopsy MeSH
• Celiac Disease * diagnosis   MeSH
• IgA Deficiency * MeSH
• Duodenum MeSH
• Cohort Studies MeSH
• Humans MeSH
• Immunologic Deficiency Syndromes MeSH
• Transglutaminases analysis   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10(-8)) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10(-11); ATG13-AMBRA1, P = 6.7 × 10(-10); AHI1, P = 8.4 × 10(-10); CLEC16A, P = 1.4 × 10(-9)) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3(+) regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P ≤ 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD.

• MeSH
• Adaptor Proteins, Signal Transducing genetics   MeSH
• Genome-Wide Association Study MeSH
• IgA Deficiency genetics   MeSH
• Genetic Variation * MeSH
• Gene Regulatory Networks MeSH
• Cohort Studies MeSH
• Lectins, C-Type genetics   MeSH
• Humans MeSH
• Monosaccharide Transport Proteins genetics   MeSH
• Autophagy-Related Proteins genetics   MeSH
• RNA, Long Noncoding genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

• Keywords
• celiakie, příčiny, screening, epidemiologie, léčba,
• MeSH
• Algorithms MeSH
• Diet, Gluten-Free MeSH
• Biopsy MeSH
• Celiac Disease * diagnosis   physiopathology   therapy   diagnosis   diet therapy   epidemiology   classification   therapy   MeSH
• IgA Deficiency MeSH
• Diagnosis, Differential MeSH
• Child MeSH
• Glutens MeSH
• HLA-DQ Antigens genetics   MeSH
• Humans MeSH
• Adolescent MeSH
• Mass Screening MeSH
• Signs and Symptoms MeSH
• Mucous Membrane pathology   MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH