Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis

A comparison of the alkaline phosphatase and immunofluorescent techniques

Davinder S. Bansi, Mario Bauducci, Annika Bergqvist, Kirsten Boberg, Ulrika Broome, Roger Chapman, Kenneth Fleming, Roberta Jorgensen, Keith Lindor, Floriano Rosina, Erik Schrumpf

Research output: Contribution to journalArticle

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Abstract

Background: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. Method: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. Patients: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. Results: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic sensitivity of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. Conclusion: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

Original languageEnglish (US)
Pages (from-to)575-580
Number of pages6
JournalEuropean Journal of Gastroenterology and Hepatology
Volume9
Issue number6
StatePublished - 1997
Externally publishedYes

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Sclerosing Cholangitis
Antineutrophil Cytoplasmic Antibodies
Phosphoric Monoester Hydrolases
Alkaline Phosphatase
Fluorescent Antibody Technique
Biliary Liver Cirrhosis
Norway
Sweden
Italy
Sensitivity and Specificity
Autoimmune Hepatitis
Healthy Volunteers
Serum
Selection Bias
Hepatitis C
Hepatitis
Liver Diseases
Neutrophils
Chronic Disease
Alcohols

Keywords

  • Antineutrophil cytoplasmic antibodies
  • Immunoalkaline phosphatase technique
  • Immunofluorescence
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis : A comparison of the alkaline phosphatase and immunofluorescent techniques. / Bansi, Davinder S.; Bauducci, Mario; Bergqvist, Annika; Boberg, Kirsten; Broome, Ulrika; Chapman, Roger; Fleming, Kenneth; Jorgensen, Roberta; Lindor, Keith; Rosina, Floriano; Schrumpf, Erik.

In: European Journal of Gastroenterology and Hepatology, Vol. 9, No. 6, 1997, p. 575-580.

Research output: Contribution to journalArticle

Bansi, DS, Bauducci, M, Bergqvist, A, Boberg, K, Broome, U, Chapman, R, Fleming, K, Jorgensen, R, Lindor, K, Rosina, F & Schrumpf, E 1997, 'Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: A comparison of the alkaline phosphatase and immunofluorescent techniques', European Journal of Gastroenterology and Hepatology, vol. 9, no. 6, pp. 575-580.
Bansi, Davinder S. ; Bauducci, Mario ; Bergqvist, Annika ; Boberg, Kirsten ; Broome, Ulrika ; Chapman, Roger ; Fleming, Kenneth ; Jorgensen, Roberta ; Lindor, Keith ; Rosina, Floriano ; Schrumpf, Erik. / Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis : A comparison of the alkaline phosphatase and immunofluorescent techniques. In: European Journal of Gastroenterology and Hepatology. 1997 ; Vol. 9, No. 6. pp. 575-580.
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abstract = "Background: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85{\%}). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. Method: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. Patients: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. Results: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71{\%} and 93{\%}, Sweden 66{\%} and 96{\%}, Norway 69{\%} and 46{\%}, Italy 50{\%} and 95{\%}. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50{\%} and 86{\%}, Sweden 56{\%} and 86{\%}, Norway 47{\%} and 61{\%}, Italy 50{\%} and 91{\%}. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66{\%} with a specificity of 74{\%} for PSC. In contrast, the IF technique gave an overall diagnostic sensitivity of only 51{\%} (P = 0.044, compared with IALP) with a specificity of 73{\%}. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. Conclusion: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26{\%} and 85{\%} may be patient related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.",
keywords = "Antineutrophil cytoplasmic antibodies, Immunoalkaline phosphatase technique, Immunofluorescence, Primary sclerosing cholangitis",
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TY - JOUR

T1 - Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis

T2 - A comparison of the alkaline phosphatase and immunofluorescent techniques

AU - Bansi, Davinder S.

AU - Bauducci, Mario

AU - Bergqvist, Annika

AU - Boberg, Kirsten

AU - Broome, Ulrika

AU - Chapman, Roger

AU - Fleming, Kenneth

AU - Jorgensen, Roberta

AU - Lindor, Keith

AU - Rosina, Floriano

AU - Schrumpf, Erik

PY - 1997

Y1 - 1997

N2 - Background: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. Method: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. Patients: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. Results: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic sensitivity of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. Conclusion: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

AB - Background: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. Method: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. Patients: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. Results: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic sensitivity of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. Conclusion: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

KW - Antineutrophil cytoplasmic antibodies

KW - Immunoalkaline phosphatase technique

KW - Immunofluorescence

KW - Primary sclerosing cholangitis

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