Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort

Abstract

Objective: To compare the performance of the American-European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren's Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems.

Methods: In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants.

Results: Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls.

Conclusions: The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.

Keywords: Classification; Diagnosis; Sjögren's syndrome.

Figure 1

Comparison of the scoring of keratoconjunctivitis sicca by the van Bijsterveld method, used in the AECG classification criteria, and the OSS (Ocular Staining Score), used in the ACR classification criteria. The van Bijsterveld score evaluates a maximum of 9 points per eye and is considered positive if at least one eye shows a score of ≥4;[24] the OSS scores a maximum of 12 points per eye evaluated and is considered positive if at least one eye shows a score of ≥3.[23] The combination of a lower cutoff level for the OSS and a higher number of possible points makes it significantly less stringent in determining that a patient has keratoconjunctivitis sicca, particularly in true Sjögren's syndrome patients (p=1×10^-6).

Figure 2

Assessment of the AECG and ACR criteria using whole-blood gene expression profiling in SS. Heat maps are displayed using fold changes for differentially expressed transcript; overexpressed transcripts (FC>0) are bright yellow, while underexpressed transcripts (FC<0) are light blue. Data is displayed in rows and columns, with rows defined by transcripts and columns defined by individual samples. Colors above each column header denote healthy controls (blue; n=73) and cases (red, yellow, or green). For cases, the represents the criteria used to define SS: red denotes cases meeting only ACR criteria (n=4); yellow denotes cases meeting only AECG criteria (n=25); and green denotes cases meeting both ACR and AECG criteria (n=127). A Sjögren's-specific set of differentially expressed (DE) transcripts was defined by comparing all SS cases regardless of classification criteria to healthy controls. Hierarchical clustering was performed with respect to transcripts and samples, and dendrograms generated to visualize sample clustering. In Panel A, all samples are displayed, with cases and controls generally segregating. In Panel B, hierarchical clustering was performed using the DE transcripts defined in Panel A, but removing cases meeting both AECG and ACR criteria. Panel C further limits the clustering to those individuals meeting only ACR or AECG. Distinct clustering of patients meeting only ACR or AECG criteria was not observed, suggesting molecular similarity between cases defined by either ACR or AECG criteria.