IU Health Pathology Laboratory
News Bulletin
June 18, 2015
DOS Updates
ATIII Funtional and ATIII Antigen—Powerchart display name change
The Cerner Powerchart display names for “ATIII Functional” and “AT III Antigen” have been updated to follow current nomenclature. The names will now display as “AT Functional” and “AT Antigen.” There have been no changes to the assays or reference ranges. Please call the special coag lab at 317-491-6000 with questions.
Factor V (Leiden) mutation, Factor II (Prothrombin) mutation, MTHFR mutation Assays
Starting May 28th the IU Health Molecular Pathology Laboratory will switch the Factor V (Leiden) mutation, Factor II
(Prothrombin) mutation and MTHFR mutation Assays to the FDA approved assays manufactured by GenMark. The eSensor
Technology uses a solid-phase electrochemical method for determining the genotyping status of a defined panel of mutations. Ordering remains the same in Cerner and collect whole blood in a 6mL Lavender (EDTA) tube. For questions about the
assay please contact Dr. Liang Cheng, medical director or the Molecular Pathology Laboratory at 317.491.6654.
HIV 1 Proviral DVA PCR QL—Discontinued test to Mayo, effective June 26. Recommended replacement in house molecular
test HIV RNA Viral Load.
Iron Ur Tm—Discontinued send out test. No replacement.
Celiac Disease Test Changes
Indiana University Health Pathology Laboratory is pleased to offer in-house serologic celiac testing, effective next week. Testing will be offered as a screening algorithm, “Celiac disease screen” or “CeliacScn”, which will begin with a determination of
the IgA concentration and initiate a testing cascade that, depending on the cascade pathway, could include the following
tests: TTG IgA, TTG IgG, Gliadin (deamidated) IgA, Gliadin (deamidated) IgG. The serologic tests will also be orderable individually. An interpretation will also be included with the cascade. Endomysial Antibodies IgA and Celiac Disease Genotyping
(HLA testing) will continue to be sendout tests.
Discontinued Cerner Test (Cerner Orderable)
Celiac Endomysial IgA
Celiac Total Serum IgA
Celiac Panel Ser QN
Gliadin Ab IgA/IgG Ser QL
Celiac Gliadin Ser IgA
Gliadin Ab IgA
Celiac Gliadin Ser IgG
Gliadin Ab IgG
Celiac TTG Serum QN
Tissue Transglutam IgA/IgG
Tissue Transglutam Ab IgA
Replaced by New Test (Cerner Orderable)
Endomysial Ab IgA Ser
Celiac Disease Screen
Celiac Disease Screen
Gliadin IgA
Gliadin IgG
Gliadin IgA
Gliadin IgA
Gliadin IgG
Gliadin IgG
TTG IgA
TTG IgG
TTG IgA
TTG IgG
TTG IgA
IU Health Pathology Laboratory
350 W 11th Street
Indianapolis, IN 46202-4108
317-491-6000 Fax: 317-491-6001 800-433-0740
www.iuhealth.org/pathologylab
Indications for testing: Patients who are symptomatic with diarrhea for greater than 4 weeks and/or other nonspecific symptoms such as fever, weight loss, skin rash, anemia, should undergo testing for celiac disease. Certain patients who may be
asymptomatic, but who are at increased risk, should also undergo testing. These include the following: first degree relatives
of individuals with biopsy-proven CD; people with type 1 diabetes mellitus and other autoimmune disorders, individuals with
Down syndrome, Turner syndrome, Williams syndrome, selective IgA deficiency, early-onset osteoporosis, among others.
Background: Celiac disease (CD) is an autoimmune disease of the small bowel characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia following exposure to glutens (prolamins and glutenins) found in wheat, barley, rye, and
oats, with histological improvement upon removal of glutens from the diet. Clinical manifestations can begin from childhood
to adulthood and can range from asymptomatic to non-specific gastrointestinal symptoms such as diarrhea, abdominal
cramping, and pain. Symptoms secondary to malabsorption such as poor growth in children, anemia, recurrent fetal loss,
osteoporosis/osteopenia are also seen. The true prevalence of CD is difficult to estimate given the varying presentations but
thought to be roughly 1% of the U.S. population. Complications include ulcerative jejunoileitis, collagenous sprue, adenocarcinomas of the small bowel, and CD-associated small intestinal T-cell lymphomas.
Testing: Diagnostic evaluation should be performed while the patient is on a gluten-containing diet. Because selective IgA
deficiency is considered to be the most common immunodeficiency worldwide with a frequency in the U.S. estimated from
1:223 to 1:1000, determination of serum IgA concentration is the initial step. Please see Table 1, algorithm, and available
testing as listed below.
While persistent elevations in serological levels may suggest inadvertent ingestion or lack of compliance with gluten-free diet,
repeat serologic testing to assess treatment response is unproven, may take a prolonged time (up to 1 year) to normalize, and
may not correlate to histological improvement. Further investigation and/or re-evaluation of patients is needed if they do not
respond to a gluten-free diet.
Genetics Genetic susceptibility is suggested by an association with certain type II human leukocyte antigens (HLA), HLA-DQ2
and HLA-DQ8. In addition, the concordance among monozygotic (identical) twins is close to 70 percent. CD affects persons of
many different ethnic backgrounds. The HLA-DQ2 allele is identified in 90-95% of patients with celiac disease with most of
the remainder having the HLA-DQ8 allele. Greater than 97% of CD individuals have the HLA-DQ2 and/or HLA-DQ8 alleles
compared to 30-40% of the general population. Therefore, an individual without the HLA-DQ2 or HLA-DQ8 allele is extremely
unlikely to have celiac disease; that is, the absence of the alleles has a high negative predictive value.
Available panel: Celiac disease screen (see algorithm below)
1. Recommended first step, unless patient is definitively known to have selective IgA deficiency a. Cerner orderable and synonyms: Celiac disease screen, CeliacScn 2. Includes serum IgA concentration with IgA anti-tTG, IgG anti-tTG, IgA anti-gliadin (deamidated), IgG anti-gliadin
(deamidated) and/or a combination, as appropriate Available in-house individual serologic tests:
1. Tissue transglutaminase (tTG) a. IgA anti-tTG ( Cerner orderable: TTG IgA) b. IgG anti-tTG (Cerner orderable: TTG IgG)
2. Anti-gliadin (deamidated) peptide a. IgA anti-gliadin(deamidated) (Cerner orderable and synonyms: Gliadin IgA or Gliadin deamidated IgA b. IgG anti-gliadin(deamidated) (Cerner orderable and synonyms: Gliadin IgG or Gliadin deamidated IgG) c. Note: Both anti-gliadin antibodies (IgA and IgG AGA) tests are no longer available Available send-out serologic test:
1. Endomysial antibody, performed by immunofluorescence microscopy, will require a separate order (Cerner orderable and synonyms: EMAIgA, Endomysial Ab IgA Ser, Endomysial Ab IgA Ser IFA) Additional testing (see algorithm):
1. Small bowel biopsy 2. Celiac HLA typing: HLA-DQ2 and HLA-DQ8 (Cerner orderable: Celiac Disease Genotyping) Table 1: Summary of test characteristics of celiac serologies, modified from Leffler and Schuppan (2010)
Test
EMA
IgA anti-tTGb
IgG anti-tTGc
IgA anti-DGP
IgG anti-DGP
IgA/IgG anti-DPG
Sensitivity
(reported range)
(%)
95 (86-100)
98 (78-100)
70 (45-95)
88 (74-100)
80 (63-95)
97 (75-99)
Specificity
(reported range)
(%)
99 (97-100)
98 (90-100)
95 (94-100)
95 (90-99)
98 (90-99)
95 (87-100)
Positive predictive valuea
(%)
83
72
42
44
68
51
Negative predictive valuea
(%)
99
99
99
99
99
99
DPG, deamidated gliadin peptide; EMA, endomysial antibody; tTG, tissue transglutaminase
a
Predictive values based on pre-test probability of 5%
b
Anti-human-tTG-based assays only; older tests based on guinea pig antibodies have lower sensitivity and specificity
c
Sensitivity is significantly higher, about 90-95%, in IgA-deficient populations but lower in the overall celiac population
References
1. Bylund DJ, Nakamura RM. Organ-Specific Autoimmune Diseases. In: McPherson RA, Pincus MR, editors. Henry’s Clinical
Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier; 2011, p 1017-1018.
2. http://www.arupconsult.com/Algorithms/CeliacDz.pdf
3. http://www.mayomedicallaboratories.com/media/articles/algorithms/1242-celiac.pdf
4. Leffler DA, Schuppan D. Update on Serologic Testing in Celiac Disease. Am J Gastroenterol. 2010;105:2520-2524.
5. NIH Consensus Development Conference on Celiac Disease. http://
consensus.nih.gov/2004/2004CeliacDisease118main.htm
6. Rostom A, Dubé C, Cranney A, et al. Celiac Disease. Summary, Evidence Report/Technology Assessment: Number 104.
AHRQ Publication Number 04-E029-1, June 2004. Agency for Healthcare Research and Quality, Rockville, MD. http://
www.ahrq.gov/clinic/epcsums/celiacsum.htm
7. Yel L. Selective IgA Deficiency. J Clin Immunol. 2010;30:10-16.