Classification criteria for Sjogren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.

https://ard.bmj.com/content/annrheumdis/61/6/554.full.pdf

Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group

The aim of the DEWS Definition and Classification Subcommittee was to provide a contemporary definition of dry eye disease, supported within a comprehensive classification framework. A new definition of dry eye was developed to reflect current understanding of the disease, and the committee recommended a three-part classification system. The first part is etiopathogenic and illustrates the multiple causes of dry eye. The second is mechanistic and shows how each cause of dry eye may act through a common pathway. It is stressed that any form of dry eye can interact with and exacerbate other forms of dry eye, as part of a vicious circle. Finally, a scheme is presented, based on the severity of the dry eye disease, which is expected to provide a rational basis for therapy. These guidelines are not intended to override the clinical assessment and judgment of an expert clinician in individual cases, but they should prove helpful in the conduct of clinical practice and research.

The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the international Dry Eye WorkShop (2007)

Summary Neuromyelitis optica (also known as Devic's disease) is an idiopathic, severe, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. Neuromyelitis optica has a worldwide distribution, poor prognosis, and has long been thought of as a variant of multiple sclerosis; however, clinical, laboratory, immunological, and pathological characteristics that distinguish it from multiple sclerosis are now recognised. The presence of a highly specific serum autoantibody marker (NMO-IgG) further differentiates neuromyelitis optica from multiple sclerosis and has helped to define a neuromyelitis optica spectrum of disorders. NMO-IgG reacts with the water channel aquaporin 4. Data suggest that autoantibodies to aquaporin 4 derived from peripheral B cells cause the activation of complement, inflammatory demyelination, and necrosis that is seen in neuromyelitis optica. The knowledge gained from further assessment of the exact role of NMO-IgG in the pathogenesis of neuromyelitis optica will provide a foundation for rational therapeutic trials for this rapidly disabling disease.

/pdf/the-spectrum-of-neuromyelitis-optica-1apj94f51h.pdf

The spectrum of neuromyelitis optica

Publisher Summary This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE). The pathogenetic mechanisms underlying murine SLE are highly complex, apparently well-programmed genetically, but still diverse and their bases not as yet well defined. Significant serologic and cellular experimental data support the statement that the final immunopathologic perturbation in murine (and human) SLE is a B lymphocyte hyperactivity with corresponding enhancement of serum antibodies and autoantibodies, particularly IgG, and consequent formation of pathogenic antigen–antibody ICs. On the basis of the available data, it appears that this B cell hyperactivity is polyclonal but not necessarily panclonal in nature, because not only antibodies against a wide array of autoantigens but also antibodies against incidental antigens, such as haptens, can be detected. The presence of autoantibodies and of their idiotypes in some recombinant lupus x normal murine lines expressing the normal partner's V genes, normal mice in which an exogenous or endogenous (Ipr gene) immunostimulator has been introduced, and unmanipulated normal mice indicate that lupus mice are not unique in their structural genetic Ig elements, whose presence determines the development of their autoimmune disease. The cause of B cell hyperactivity in lupus has not yet been fully elucidated. Autonomous B cell maturation does not appear likely, because B cell proliferation and differentiation in lupus mice was found to be dependent on the same number of accessory signals as in normal mice.

Murine models of systemic lupus erythematosus.

Sjögren's syndrome

The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkin's lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenstrom's macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.

Increased Risk of Lymphoma in Sicca Syndrome

Sjogren syndrome (SS) is a common autoimmune disease evidenced by broad organ-specific and systemic manifestations, the most prevalent being diminished lacrimal and salivary gland function, xerostomia, keratoconjunctivitis sicca, and parotid gland enlargement. Primary SS presents alone, and secondary SS occurs in connection with autoimmune rheumatic diseases. In addition, symptoms do not always present concurrently. This diversity of symptomatic expression adds to the difficulty in initial diagnosis. Armed with the recently refined criteria for diagnosis, specialists, such as rheumatologists, primary care physicians, ophthalmologists, and dentists, who would otherwise focus only on those symptoms that encompass their areas of expertise, can get a comprehensive image of the presenting patient, leading to earlier identification and treatment of SS.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/217138/ira30008.pdf

Clinical Manifestations and Early Diagnosis of Sjogren Syndrome

We have developed a highly specific and sensitive "two-site" immunoradiometric assay for murine IgM in which antigen bound to immobilized antibody reacts with affinity-purified radiolabeled antibody. We utilized the sensitivity of this assay to study the rate of IgM secretion in short-term cultures by spleen cells from the autoimmune strains, New Zealand Black (NZB) and New Zealand Black by New Zealand White F1 hybrid (BW), and from normal (C57BL/6, DBA/2, NZW) mice. The temperature dependence of IgM secretion in short-term cultures, its pentameric structure, and the similar viability of NZB and normal strain spleen cells indicate that active IgM synthesis is being measured. We observed that the splenic B lymphocytes of NZB and BW mice, in contrast to normal strains, produce IgM in vitro at birth. By 6 to 8 weeks of age NZB and BW spleen cells produce 40 times more IgM than spleen cells from normal strains of mice. The IgM produced in vitro by splenic lymphocytes from NZB and BW mice is not absorbed by synegeneic or allogeneic thymocytes or erythrocytes.

Demonstration of Activation of B Lymphocytes in New Zealand Black Mice at Birth by an Immunoradiometric Assay for Murine IgM

Sjogren's syndrome is associated with a serologically defined histocompatibility antigen of the HLA-B locus, HLA-B8. Another closely linked locus, HLA-D, determines lymphocyte-defined cell-surface antigens. In laboratory animals such antigens are closely linked to immune response genes. To determine whether Sjogren's syndrome is primarily associated with an HLA-D antigent or with HLA-A and HLA-B antigens as well as HLA-Dw3, which is known to be in linkage disequilibrium with HLA-B8. We found the primary association of association of Sjogren's syndrome to be with HLA-Dw3, which we observed in 84 percent of patients with Sjogren's syndrome in the absence of rheumatoid arthritis as compared to 24 percent in controls (P less than 0.00001). The frequency of HLA-B8 and HLA-Dw3 in patients with both Sjogren's syndrome and rheumatoid arthritis did not differ from that in controls. Patients with Sjogren's syndrome and rheumatoid arthritis comprise genetically distinct groups.

https://www.nejm.org/doi/pdf/10.1056/NEJM197704212961602?listPDF=true

Stuart S. Kassan

Papers

Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group

Increased Risk of Lymphoma in Sicca Syndrome

Clinical Manifestations and Early Diagnosis of Sjogren Syndrome

Demonstration of Activation of B Lymphocytes in New Zealand Black Mice at Birth by an Immunoradiometric Assay for Murine IgM

Sjögren's syndrome association with HLA-Dw3.