Ava J. Wu

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

We propose new classification criteria for Sjögrens syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.

Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjogren's syndrome among 1,726 registry participants.

OBJECTIVE To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögrens syndrome (SS). METHODS The database of the Sjögrens International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features. RESULTS LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS. CONCLUSION Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.

Polyreactive antigen‐binding B cells are the predominant cell type in the newborn B cell repertoire

Polyreactive antibodies bind to a variety of different self and non‐self antigens. The B cells that make these antibodies express the polyreactive Ig receptor on their surface. To determine the frequency of polyreactive antigen‐binding B cells in peripheral blood, we incubated two different antigens, one (insulin) labeled with fluorescein isothiocyanate and the other (β‐galactosidase) with phycoerythrin, with peripheral B cells. The percentage of cells that bound these antigens was determined with the fluorescence‐activated cell sorter. Approximately 21 % of adult B cells bound insulin, 28 % bound β‐galactosidase, and 11 % bound both antigens. In contrast to B cells in the adult repertoire, 49 % of B cells in cord blood bound insulin, 54 % bound β‐galactosidase, and 33 % bound both antigens. The properties of polyreactive antigen‐binding B cells in adult and cord blood were similar, except for the fact that almost all the polyreactive antigen‐binding B cells in cord blood were CD5 positive (93 %), whereas only 40 % of the polyreactive antigen‐binding B cells in adult peripheral blood were CD5 positive, indicating that the CD5 marker is not directly linked to polyreactivity. The percentage of polyreactive antigen‐binding B cells in patients with Sjögrens syndrome, systemic lupus erythematosus and rheumatoid arthritis was equal to or slightly below that found in the normal adult B cell repertoire. It is concluded that polyreactive antigen‐binding B cells are a major constituent of the normal adult B cell repertoire and are the predominant cell type in the newborn B cell repertoire.

Small Proline-Rich Protein 1B (SPRR1B) Is a Biomarker for Squamous Metaplasia in Dry Eye Disease

PURPOSE Squamous metaplasia occurs in ocular surface diseases like Sjögrens syndrome (SS). It is a phenotypic change whereby epithelial cells initiate synthesis of squamous cell-specific proteins such as small proline-rich protein 1B (SPRR1B) that result in pathologic keratin formation on the ocular surface. The authors hypothesized that inflammation is a key inducer of pathologic keratinization and that SPRR1B represents an analytical biomarker for the study of the molecular mechanisms. METHODS Real-time quantitative RT-PCR and immunohistochemistry were used to examine SPRR1B mRNA and protein in two different mouse models of dry eye and patients with SS. Adoptive transfer of mature lymphocytes from mice lacking the autoimmune regulator (aire) gene was performed to examine the role of inflammation as an inducer of squamous metaplasia. SPRR1B expression in response to several cytokines was examined in vitro, whereas the expression of cytokines IL1beta and IFNgamma was quantified in ocular tissues of aire-deficient mice and patients with SS. RESULTS SPRR1B was increased across the ocular surface of mice with both desiccating stress and autoimmune-mediated, aqueous-deficient dry eye and in patients with SS. Adoptive transfer of CD4(+) T cells from aire-deficient mice to immunodeficient recipients caused advanced ocular surface keratinization. IL1alpha, IL1beta, IL6, IFNgamma, and TNFalpha induced SPRR1B expression in vitro and the local expression of IL1beta and IFNgamma was elevated in ocular tissues of patients with SS and aire-deficient mice. CONCLUSIONS SPRR1B is a valid biomarker for the study of the molecular mechanisms of squamous metaplasia. There is a definitive link between inflammation and squamous metaplasia in autoimmune-mediated dry eye disease, with IL1beta and IFNgamma likely acting as key participants.

Optimizing dry mouth treatment for individuals with Sjögren's syndrome.

A hallmark of the oral component of Sjögrens syndrome (SS) is the complaint of dry mouth thought to be secondary to dysfunction of the salivary glands. This article describes how treatment may be optimized for individuals who have dry mouth.

Sjögren's syndrome.

This article reviews the diagnostic criteria for Sjorgens syndrome (SS), as well as some of the more common associated signs and symptoms. Dermatological manifestations associated with SS will be evaluated. Finally, general treatment strategies will be discussed.

Treatment of primary Sjogren's syndrome with low-dose natural human interferon-α administered by the oral mucosal route

The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögrens syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögrens syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.