The measurement of serum salivary isoamylase as a clinical parameter in Sjögren's syndrome

W. W. I. Kalk, A. Vissink, J. C. J. M. Swaanenburg1, F. K. L. Spijkervet, J. L. N. Roodenburg, H. Bootsma2 and C. G. M. Kallenberg3

Departments of Oral and Maxillofacial Surgery,
1 Pathology and Laboratory Medicine,
2 Rheumatology and
3 Clinical Immunology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

SIR, Exocrine gland damage due to chronic autoimmune inflammation in Sjögren's syndrome (SS) can be demonstrated, hypothetically, by an increase in gland-specific enzymes that are released in serum, as an alternative to current diagnostic techniques demonstrating loss of function or change in architecture. Measurement of serum enzymes to estimate glandular damage is not used routinely in SS patients, despite the fact that the major salivary glands contain large amounts of salivary (S) isoamylase and are invariably involved in the disease process of SS [13]. The objective of this study was to determine the clinical value of serum measurement of isoamylases in SS.

One hundred consecutive patients referred for diagnosis of SS in the period from January 1998 until January 2000 were included in the study. Patients were categorized by diagnosis (positive or negative) according to the revised European classification criteria for SS [4, 5]. In addition to the diagnostic tests for SS, serum isoamylases were measured. S-isoamylase activity was calculated from total amylase and pancreatic (P) isoamylase activities. P-isoamylase activity was determined after inhibition of S-isoamylase activity with a monoclonal antibody (catalogue no. 1660764; Roche, Germany). The duration of oral symptoms, defined as the time from the first complaint of oral dryness until referral, was also assessed. Acute pancreatitis, gall-bladder disease, acute parotitis and alcohol abuse were used as exclusion criteria. Data were submitted to statistical analysis with MedCalc version 5.0 in order to calculate receiver operating characteristic (ROC) curves and the Statistical Package for the Social Sciences (SPSS; SPSS Inc., IL, USA) version 9.0 for the remaining statistical procedures [6].

Thirty-seven patients were categorized as SS [22 primary and 15 secondary SS; male:female ratio 1:18, mean age 57 (±13) yr] and 63 patients as non-SS (male:female ratio 1:31, mean age 54 (±12) yr]. The mean (S.D.) total amylase activity in the group of 37 SS patients significantly exceeded the corresponding activity for the 63 non-SS patients [SS, 184 (±92) U/l; non-SS, 146 (±58) U/l; P<0.05, t-test], mainly due to an increase in S-isoamylase activity. Thirty-five per cent of the SS patients showed elevated S-isoamylase activity (normally <=105 U/l) compared with 14% of the non-SS patients. P-isoamylase activity (normally <=115 U/l) was elevated in 14% of the patients in both groups. ROC curve analysis of S-isoamylase activity revealed an optimum threshold for differentiating SS from non-SS at 106 U/l (close to the normal threshold value) with a likelihood ratio of 3.2 (specificity 89%, sensitivity 35%). In SS patients, serum S-isoamylase activity correlated inversely with the duration of oral symptoms prior to referral (rpearson=-0.33, P=0.05), which averaged 29 months for both groups. The SS patients with high S-isoamylase activity (above the normal range) had a much shorter duration of oral symptoms (mean 11 months) than the SS patients with normal S-isoamylase activity (mean 35 months), whereas the SS patients with low S-isoamylase activity (less than one standard deviation below the mean) had a much longer duration of oral symptoms (mean 49 months) (Fig. 1Go). These differences proved statistically significant in one-way analysis of variance. Furthermore, the serum S-isoamylase activity of SS patients correlated significantly with salivary sodium and chloride concentrations (also after correction for salivary flow rates), which are related to inflammation of the salivary glands [7].



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FIG. 1.  S-isoamylase activity (U/l, mean±S.D.) vs duration of xerostomia in SS.

 
The results of this prospective clinical study show that serum isoamylase measurement may be useful in monitoring disease progression in SS, but that it has limited diagnostic value. The observation that high serum S-isoamylase activity in SS patients corresponded with a relatively short duration of oral symptoms (<1 yr) suggests that initial salivary gland involvement is reflected in high amylase activity, which is in accordance with the literature [8]. In the advanced phase, the enzyme leakage in serum seems to have ceased (Fig. 1Go). In a previous study it was demonstrated that sialometry and sialochemistry are useful in staging the oral manifestation of SS [9], and this also appears to be valid for serum S-isoamylase activity. The biphasic course of enzymatic activity, in terms of time, in SS patients may well explain its low sensitivity for diagnosing SS, because patients beyond the initial phase of intracellular enzyme leakage cannot be recognized enzymatically. Interestingly, the amount of serum amylase leakage in SS (resulting from increased cell death) correlated significantly with the disturbance of the sialochemical variables sodium and chloride, which is characteristic of salivary gland inflammation in SS [7, 10]. Therefore, S-isoamylase in serum may be informative regarding disease activity and the prognosis of salivary gland function: high serum S-isoamylase activity may indicate active disease at the glandular level (relatively rapid deterioration of secretory functions), normal activity a more stable situation, but low activity an end situation with little change to be expected in secretory function. In order to verify such considerations regarding outcome variables in SS, a long-term prospective study is warranted.

The advice and support of Dr L. F. E. Michels (oral and maxillofacial surgeon) and Dr K. Mansour (ophthalmologist, University Hospital Groningen) are gratefully acknowledged.

Notes

Correspondence to: W. W. I. Kalk, Department of Oral and Maxillofacial Surgery, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. Back

References

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Accepted 28 December 2001





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