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ID PMID Title PublicationDate abstract
14523226 Serum MMP-1 and TIMP-1 levels are increased in patients with psoriatic arthritis and their 2004 Mar OBJECTIVE: To determine matrix metalloproteinase-1 (MMP-1) and tissue-inhibitor metalloproteinase-1 (TIMP-1) serum levels in patients with psoriatic arthritis (PsA) and to compare this with their siblings and local blood donor controls. PsA is an interesting condition in which to study metalloproteinases because there are variations in the level of destructiveness, including a significant proportion of cases without destructive change. This is unlike rheumatoid arthritis (RA) which is more uniformly destructive and where MMP-1/TIMP-1 levels are known to be elevated. METHODS: MMP-1 and TIMP-1 serum levels were determined by enzyme-linked immunosorbent assay (ELISA) in (a) index cases with PsA (subtype: RA n = 43, distal interphalangeal disease n = 2, oligoarticular n = 15, spondyloarthropathy n = 9, enthesitis n = 1), (b) siblings with PsA, (c) siblings with psoriasis (Ps), (d) unaffected siblings and (e) local controls. Patients with Ps were divided according to the onset of disease: type I disease, onset before age 40 yr and type II, onset after age 40 yr. RESULTS: MMP-1 and TIMP-1 levels were significantly increased in both the index cases and the group including all siblings compared with the controls (P < 0.0001). There was no statistical difference in MMP-1 or TIMP-1 levels between index cases and their siblings. There was no difference in serum MMP-1 level between the different subtypes (Moll and Wright) of PsA, but there was an increased level of serum TIMP-1 in patients with rheumatoid pattern (P = 0.05). In the index cases there were increased levels of TIMP-1 in type II onset psoriasis (P = 0.03) but no difference in MMP-1 levels. CONCLUSION: MMP-1 and TIMP-1 serum levels are elevated in PsA. This is greatest in RA pattern PsA. These levels were also elevated in unaffected siblings suggesting that genetic factors may be important. TIMP-1 levels were elevated in psoriasis alone, more so in late onset psoriasis, suggesting that the pathological processes of early and late onset psoriasis may be different.
11824957 A prospective population based study on outcome of juvenile chronic arthritis in Costa Ric 2002 Jan OBJECTIVE: To study the disease process and outcome in an unselected group of patients with juvenile chronic arthritis (JCA). METHODS: From a population based study in San José, Costa Rica, 47 patients with JCA with disease onset from 1993 through 1995 were investigated after median duration of 4.1 yrs (range 2.9-4.9) (incidence group). Another 49 children with disease onset prior to 1993 and younger than 16 years of age on December 31, 1995 (cross sectional group) were also followed. RESULTS: In the incidence group, 4/47 children changed subtype during the course of the disease. All did so within 2 years from disease onset, and the same observation was made in the cross sectional group. Uveitis was described at onset in a single case, and no child developed uveitis later. In patients from the incidence group in the process of being transferred to adult rheumatology clinics, 48% were still taking medication. Patients who had involvement of proximal interphalangeal (PIP) joints at onset had an increased risk of being active or stable at followup (RR 12.3, 95% CI 1.4-108.3). A higher chance of no continuing disease activity at followup was observed in children with oligoarticular disease than in the other subtypes (RR 2.8, 95% CI 1.2-6.9). CONCLUSION: Uveitis associated with antinuclear antibody positive JCA and psoriatic arthritis in Costa Rican children is uncommon, and the risk of developing uveitis remains low during the course of the disease. Involvement of PIP joints predicts an increased risk of continuing disease. The course of JCA in Costa Rican children is not milder than in Caucasian populations, since 48% of the patients showed persistent disease activity at the transition to adult care.
12173279 The prevalence and burden of arthritis. 2002 Apr The prevalence of arthritis is high, with osteoarthritis (OA) being one of the most frequent disorders in the population. In England and Wales, between 1.3 and 1.75 million people have OA and a further 0.25-0.5 million have rheumatoid arthritis (RA), while in France some 6 million new diagnoses of OA are made each year. In 1997, approximately 16% of the US population had some form of arthritis. This prevalence is expected to increase in the coming years, as arthritis more often affects the elderly, a proportion of the population that is increasing. The economic burden of such musculoskeletal diseases is also high, accounting for up to 1-2.5% of the gross national product of western nations. This burden comprises both the direct costs of medical interventions and indirect costs, such as premature mortality and chronic and short-term disability. The impact of arthritis on quality of life is of particular importance. Musculoskeletal disorders are associated with some of the poorest quality-of-life issues, particularly in terms of bodily pain (mean score from the MOS 36-item Short Form Health Survey of 52.1) and physical functioning (49.9), where quality of life is lower than that for gastrointestinal conditions (bodily pain 52.9, physical functioning 55.4), chronic respiratory diseases (72.7, 65.4) and cardiovascular conditions (64.7, 59.3).
12100468 Immune regulation in adjuvant disease and other arthritis models: relevance to pathogenesi 2002 Jul Experimental models of arthritis and their human counterparts fall into three distinct classes: (a) responses of T cells to disseminated microbial antigens (Ags) as such; (b) responses of T cells to cartilage autoAgs; and (c) responses of T cells to major histocompatibility complex (HLA-B27, DRB1) or other membrane components (LFA-1) expressed on bone marrow-derived cells. The primary immune response is driven, in naturally occurring disease, by microbial infection, e.g. with streptococci, enteric gram-negative rods or spirochetes, or is experimentally induced with mycobacterial and other adjuvants. The response to cartilage components, such as collagen type-II and various proteoglycans, may be driven by cross-reactive microbial Ags, heat shock proteins (HSPs) in particular, or the adjuvant effect of intense primary joint inflammation, as in rheumatoid arthritis and the spondyloarthropathies. Adjuvant disease appears to be purely T-cell-mediated, whereas both T cells and antibody play a role in collagen and many other forms of arthritis. Experimental evidence suggests a pathogenetic role for T-cell receptor gammadelta T cells in some lesions. Arthritis may be regulated by microbial and tissue HSPs, when these are administered by a nonimmunizing route or as altered peptide ligands, by anti-idiotypic responses that block the action of effector T cells, and by competing Ags. Immune regulation involving natural killer (NK), NK T and certain subsets of gammadelta and alphabeta T cells, which may affect the occurrence, localization and character of this group of diseases, presents a challenge for further investigation.
15552509 Undifferentiated arthritis--disease course assessed in several inception cohorts. 2004 Sep The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Because early aggressive treatment might offer an effective means to slow disease progression in RA, it is important to identify UA patients who will develop RA and treat them as early as possible. At the same time, inappropriate treatment of patients with a more benign disease course should be avoided. Here, an overview is given of the characteristics and numbers of patients with UA who evolve into RA. UA is defined as any arthritis that has the potential for a persistent course, without fulfilling the classification criteria for specific rheumatic disorders. To compare endpoints in the different databases, the 1987 ACR criteria for RA were used. In the nine databases employing a similar definition for undifferentiated arthritis, the proportion of patients with UA that evolved into RA within 1 year varied from 6% to 55%. These differences arise in large part from differences in the inclusion criteria and in the definitions used for UA and RA. The data from the various cohorts support a hypothesis that a considerable proportion of UA patients are actually patients with RA in a very early stage. Controlled intervention studies with early antirheumatic treatment in these patients are mandatory in order to provide further insight into the natural course of UA and to define a treatment strategy that will successfully slow or prevent disease progression.
14770092 Outcome measurement: health status and quality of life. 2004 Mar Measures of health-related quality of life, which assess patients' symptoms, their functioning, and their satisfaction with their health status, have received increased attention. Quality-of-life measures specifically developed for patients with rheumatoid arthritis and ankylosing spondylitis have been reported, and generic quality-of-life measures have been validated in patients with diverse rheumatic diseases. Although many studies have assessed the psychometric properties of health status measures, few studies have focused on the interpretation and meaning of questionnaire results. New measures should identify the unique role they occupy in patient assessment.
12683424 Clinical profiles of celecoxib and rofecoxib in the rheumatic diseases. 2002 Sep Celecoxib and rofecoxib are highly specific cyclooxygenase-2 inhibitors. Both agents are as effective as conventional, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) but they have a markedly reduced propensity to cause injury to the gastroduodenal mucosa compared with conventional NSAIDs. Celecoxib and rofecoxib are approved for treatment of both osteoarthritis and rheumatoid arthritis. This presentation reviews the mechanism of action of these agents, the clinical studies showing their effectiveness for treatment of arthritis, and the gastrointestinal side effect profiles compared with conventional NSAIDs.
15248235 Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced a 2004 Jul OBJECTIVE: To study the effect of zoledronic acid (ZA) on synovial inflammation, structural joint damage, and bone metabolism in rats during the effector phase of collagen-induced arthritis (CIA). METHODS: CIA was induced in female dark agouti rats. At the clinical onset of CIA, rats were assigned to treatment with vehicle or single subcutaneous doses of ZA (1.0, 10, 50, or 100 microg/kg). Clinical signs in all 4 paws were scored on a daily basis. After 2 weeks, the joints in the hind paws were assessed using plain radiographs, microfocal computed tomography (micro-CT), histologic scoring, and histomorphometry, and the serum levels of type I collagen crosslinks were measured by enzyme-linked immunosorbent assay. RESULTS: Although ZA mildly exacerbated synovitis, it effectively suppressed structural joint damage. At doses of >/=10 microg/kg, ZA significantly reduced radiographic bone erosions, Larsen scores, and juxtaarticular trabecular bone loss as quantified by micro-CT. ZA prevented increased type I collagen (bone) breakdown in CIA and diminished histologic scores of focal bone erosion by up to 80%. Increases in the percentage of eroded surface, osteoclast surface, and osteoclast numbers associated with CIA were prevented by ZA, even though synovitis scores were unchanged. CONCLUSION: Single doses (>/=10 microg/kg) of ZA strikingly reduced focal bone erosions and juxtaarticular trabecular bone loss, although synovitis was mildly exacerbated. Targeting osteoclasts with ZA may therefore be an effective strategy for preventing structural joint damage in rheumatoid arthritis.
15145425 Glenohumeral arthritis and its management. 2004 May Glenohumeral arthritis has many different etiologies, including osteo-arthritis, secondary degenerative joint disease, rheumatoid arthritis,avascular necrosis, cuff tear arthropathy, and capsulorrhaphy arthropathy. Each of these diagnoses may have different underlying pathoanatomy and pathomechanics. The treating physician must recognize how these characteristics impair shoulder function so that the prescribed course of treatment addresses the root causes of shoulder dysfunction. The patient's age. level of physical activity, and comorbidities should be taken into account, and the intended management should be weighed against how these factors may interfere with treatment efficacy over the long-term. The goal of treatment is to restore comfort, motion, strength, and stability to the shoulder in a safe and reliable manner. Conservative treatments should aim to optimize shoulder flexibility, maintain muscle function, and reduce inflammation. Activity modification is crucial but often unreasonable to the active patient. Temporary surgical approaches include arthroscopic debridement and synovectomy. These approaches may be appropriate for a younger patient with some remaining joint space and a functional rotator cuff. Definitive surgical treatment typically involves either a proximal humerus replace mentor a total shoulder replacement. The decision to resurface the glenoid should be based on the patient's age, diagnosis, available bone stock, and physical demands. The surgeon must be familiar with the options provided by the given implant system so that the proper balance of motion and stability can be restored with a close approximation of the native anatomy. Inexperienced hands, good-to-excellent results can be achieved in greater than 90% of properly selected patients. Glenoid component failure is one of the most common complications of shoulder arthroplasty, highlighting the need to select carefully patients in whom glenoid resurfacing is warranted.
12022326 High response rate in the phase I/II study of meloxicam in juvenile rheumatoid arthritis. 2002 May OBJECTIVE: Use of meloxicam as a selective COX-2 inhibitor for treatment of adult rheumatic diseases decreases the frequency of gastrointestinal (GI) side effects in comparison with nonselective COX inhibitors. Up to 50% of children with juvenile rheumatoid arthritis (JRA) also develop GI side effects through nonselective COX inhibitors. In this 12 week Phase I/II study, with an additional open extension lasting up to 52 weeks, the safety, efficacy, and pharmacokinetics of meloxicam in JRA were investigated. METHODS: Meloxicam suspension 0.25 mg/kg once daily was given to 36 patients with JRA who required a nonsteroidal antiinflammatory drug. Safety evaluation and periodic measurement of efficacy were carried out using the Pediatric Rheumatology International Trials Organisation (PRINTO) criteria. Eighteen patients underwent pharmacokinetic (PK) evaluation. RESULTS: Thirty-one patients completed the study. Four were dropped due to administrative reasons. One patient, who found the drug ineffective, discontinued participation. A response was seen according to PRINTO outcome criteria in 44% of the patients at Week 4, 62% at Week 12, and 74% at Week 52. Drug related adverse events were observed in 5 patients. PK evaluation showed that the maximum plasma concentration Cmax of -34% and AUC(0-infinity) of -28% tended to be lower in younger children (2-6 years) versus older children. Plasma elimination half-life (13 h) was similar in all patients. CONCLUSION: Meloxicam suspension 0.25 mg/kg once daily seems to be effective and safe for treating active JRA over a period of 52 weeks.
11966758 The arthritogenic adjuvant squalene does not accumulate in joints, but gives rise to patho 2002 Mar A single intradermal injection of the adjuvant-oil squalene induces T cell-mediated arthritis in DA rats. The chain of events leading from non-specific provocation of the immune system to arthritis, with clinical similarities to rheumatoid arthritis, is largely undetermined. Here, we combined in vivo tracking of tritium-labelled squalene with lymph node (LN) cell transfer experiments to determine where critical activation events may take place. The majority of squalene remained at the injection site (79%). The amounts recovered in peripheral joints (<1%) were equal to that recovered in other organs that can be targets in autoimmune diseases. This argues that arthritis does not develop as a consequence of adjuvant accumulation in joints. In contrast, substantial amounts of squalene were recovered in hyperplastic LN draining the injection site (1-13%). The adjuvant was deposited to a larger extent in cells than in extracellular matrix. The draining LN cells could transfer arthritis to naïve irradiated DA rats following in vitro stimulation with conA. Interestingly, non-draining LN were also hyperplastic and harboured arthritogenic cells, although they contained low amounts of squalene (<1%). Consequently, the amount of arthritogenic adjuvant in a particular LN is not closely linked to the development of pathogenic cells. The distribution pattern of squalene was similar in MHC-identical but arthritis-resistant PVG.1AV1 and LEW.1AV1 rats, and it was unaffected by T cell depletion with a monoclonal antibody (R73). Thus, T cells and non-MHC genes do not regulate dissemination of squalene, but rather determine arthritis development at the level of adjuvant response.
11920417 Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced ar 2002 Mar OBJECTIVE: To determine the efficacy of local therapy with human angiostatin gene in murine collagen-induced arthritis (CIA). METHODS: DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatin-expressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin-1 beta. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti-CD31 antibody and measurement of von Willebrand factor levels. RESULTS: Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin-expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritis-associated angiogenesis. CONCLUSION: Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.
15559647 Juvenile arthritis-associated uveitis: visual outcomes and prognosis. 2004 Oct BACKGROUND: The current issues in the management of uveitis associated with juvenile arthritis revolve mainly around the treatment of mild disease and how to treat patients with more severe disease. The aims of this study were to determine the incidence of uveitis in a cohort of patients with juvenile arthritis as well as the nature of treatment and the risk factors for visual loss. METHODS: Review of the charts of 71 patients with juvenile arthritis, as defined by the American Academy of Rheumatology, seen between 1992 and 2001 at a combined rheumatology and ophthalmology clinic. Information collected included the patient's sex, age at diagnosis of arthritis and uveitis, and date of diagnosis of arthritis and uveitis. The rheumatologic diagnosis, results of serologic testing, and details of systemic and topical treatments were also recorded. RESULTS: There were 47 girls and 24 boys ranging in age from 16 months to 13 years. The median age at diagnosis of juvenile arthritis was 4 years and 1 month. Twenty-seven patients (38%) had uveitis. The median age at uveitis onset was 5.9 years, with an average interval of 18 months from the diagnosis of arthritis; 11 patients had uveitis at the time of arthritis diagnosis. There was a positive relation between anti-nuclear antibody positivity and the development of uveitis (p < 0.05). Thirteen (48%) of the 27 patients with uveitis had mild anterior segment inflammation, with fewer than 25 cells in the anterior chamber. This group had spontaneous resolution of uveitis without topical therapy. All the patients without uveitis had a final visual acuity of 6/9 or better. Five of the patients with uveitis had a final visual acuity of 6/36 or worse. Cataract was the most common complication affecting visual outcome. Cataract extraction initially improved the visual acuity, but posterior segment complications and glaucoma compromised the final visual outcome. INTERPRETATION: We found an incidence of uveitis of 38% with long-term follow-up of patients with juvenile arthritis; the uveitis was diagnosed an average of 18 months after the arthritis. Almost half of the patients with uveitis had minor anterior segment inflammation. These patients did not receive topical treatment and had good visual outcomes. Patients with uveitis at the time of diagnosis of arthritis tended to have a worse visual prognosis and experienced persistent uveitis despite treatment. In this series, cataract extraction was beneficial in improving visual acuity immediately postoperatively, but posterior segment changes and glaucoma may compromise final visual outcomes.
12470760 Multifocal choroiditis in patients with familial juvenile systemic granulomatosis. 2002 Dec PURPOSE: To document clinical features of uveitis in patients with familial juvenile systemic granulomatosis. DESIGN: Retrospective chart review. METHODS: Ophthalmologic examination, medical history, and clinical course in 16 patients from eight families examined at six academic medical centers. RESULTS: Of the 16 patients, 15 had evidence of panuveitis with multifocal choroiditis. One patient had only an anterior uveitis. Ischemic optic neuropathy, presumably due to a small vessel vasculopathy, and retinal vasculopathy each occurred in one patient. Ocular complications were common, including cataracts in 11, glaucoma in six, band keratopathy in six, cystoid macular edema in six, and optic disk edema in six. All 16 patients had polyarthritis, and at least nine had skin rash. Often patients were misdiagnosed initially as having either juvenile rheumatoid arthritis or sarcoidosis. CONCLUSIONS: Familial juvenile systemic granulomatosis is an uncommon genetic disease characterized by polyarthritis and uveitis. Panuveitis and multifocal choroiditis often may be present. Patients with a diagnosis of juvenile rheumatoid arthritis but having a family history of the disease and multifocal choroiditis should be suspected of having familial juvenile systemic granulomatosis.
12624805 Measurement of disease activity in psoriatic arthritis. Extended report. 2003 Feb OBJECTIVE: To determine whether activity indices, generally accepted in rheumatoid arthritis (RA) are useful and valid to measure disease activity in psoriatic arthritis (PsA) patients with peripheral arthritis. METHODS: 38 PsA patients were studied before and after a one year DMARD treatment. Extended and reduced tender and swollen joint counts, Ritchie articular index, Health Assessment Questionnaire HAQ) score, erythrocyte sedimentation rate (ESR) morning stiffness, the patient's and the assessor's global assessment (PGA and AGA) were recorded. Disease activity scores, EULAR, ACR and Clegg improvement criteria were calculated. RESULTS: All indices correlated well before and after treatment with AGA (r > 0.337, p < 0.042), except morning stiffness and tender joint counts. After treatment, PGA correlated well only with the 68 and 28 tender joint counts, ESR and HAQ (r > 0.340, p < 0.05). The response to DMARD treatment was well characterized with the changes in the number of tender and swollen joint counts, and DAS4, DAS3, DAS28. The changes correlated with the PGA and AGA. The level of agreement between Clegg and the EULAR improvement criteria with both extended and reduced joint count was comparable (p < 0.01). CONCLUSION: The well-known activity indices generally accepted in RA, as tender and swollen joint count, DAS3, DAS4, DAS28, are useful and valid indices measuring arthritis activity in PsA with peripheral arthritis. The correlation between Clegg and EULAR improvement classification indices were similar. Both seemed to characterize changes authenticated during DMARD treatment.
15611681 [Ankylosing spondylitis]. 2004 Nov 20 A FREQUENT AFFECTION: Ankylosing spondylitis is a chronic inflammatory rheumatism usually affecting young adults and characterized by an inflammatory enthesiopathy progressing towards ossification and ankylosis. It is ranked in second position of chronic inflammatory rheumatism, after rheumatoid arthritis. IMPROVING ITS EVOLUTION: Early diagnosis and adapted therapy would contribute in improving its prognosis and avoid the evolution to severe forms of the disease. RECENT PROGRESS: The recent advances in this disease are the enhanced knowledge of its physiopathology and the development of efficient drugs (anti-TNFalpha).
14611119 Non-HLA gene polymorphisms in juvenile rheumatoid arthritis. 2003 Sep A substantial amount of work has gone into elucidating the non-HLA genetic associations in JRA. In this paper, we attempt to provide an overview of this body of knowledge. Direct comparison of the different studies is difficult. Different ethnic populations, different JRA/JIA subgroups, and different systems of nomenclature and classification all impose various limitations. Adding to the complexity is the polygenic nature of chronic childhood arthritis. Family based studies will be necessary to overcome ethnicity related issues. A candidate gene approach complemented by genome wide screen data will hopefully advance our knowledge of the genetics of JRA.
17028800 Recombinant adeno-associated virus preferentially transduces human, compared to mouse, syn 2004 Despite a number of published reports, including from our own laboratory, suggesting that adeno-associated virus (AAV) transduces mouse synovium, a careful analysis demonstrated transduction predominantly of the subsynovial muscle tissue, while the synovial lining is poorly transduced. To investigate the potential of AAV to transduce human synovium, three human rheumatoid arthritis (RA) and two murine collagen-induced arthritis (CIA) synovial cell lines were infected with recombinant AAV (rAAV) vectors encoding either mouse IL-10 or IL-4. Low-level transgene expression was observed. However, either Gamma-irradiation or the addition of a low-titer E1-, E3-deleted recombinant adenovirus resulted in up to a 100-fold increase in transgene product in the human, but not the mouse, cell lines. RA synovial tissues implanted subcutaneously in severe combined immunodeficiency (SCID) mice, which were subsequently infected with rAAV, showed marked increases in transgene expression when co-infected with adenovirus. To our knowledge, this is the first study to show that intact human synovial tissues can be transduced by rAAV, and it suggests that murine arthritis may not be an optimal model to study rAAV as a gene transfer vector. Further studies to elucidate the mechanisms limiting gene transduction in human synovium may allow optimization of this vector for the treatment of arthritis.
12219648 [Prosthesis implantation in the proximal ankle joint--a real therapeutic alternative in po 2002 Jul The results of total ankle arthroplasty were poor in the 1970s and 1980s compared to those of the arthrodeses. Because of the good long term results this technique has been accepted as the treatment of the choice for posttraumatic arthritis of the ankle. Recently the development of an unconstrained total ankle arthroplasty with an additional mobile polyethylene inlay between the fixed tibial and the talar component which enables a three dimensional range of motion seems to improve significantly the long term results of total ankle replacement. This technique, however, is an extremely demanding procedure. The range of motion after total ankle replacement following posttraumatic arthritis is poor compared to the results of total ankle replacement for rheumatoid arthritis. Furthermore, these data are obtained yet only by a few experienced surgeons in specialized centers. Further clinical trials have to be performed to answer the question whether the total ankle arthroplasty is a reliable alternative treatment of posttraumatic arthritis of the ankle. At present, the arthrodesis should be regarded as the treatment of choice for the posttraumatic arthritis of the ankle joint.
12383988 Primary Sjögren's syndrome and deficiency of ICA69. 2002 Oct 5 BACKGROUND: Sjögren's syndrome is a common (about 1% of the population) autoimmune disease of salivary and lacrimal glands. Its cause and pathogenesis are poorly understood, and treatments are mostly for symptoms of the disease. ICA69 is a self-antigen expressed in brain, pancreas, salivary, and lacrimal glands. NOD-strain mice are an animal model of spontaneous Sjögren's syndrome. We aimed to assess the role of ICA69 in autoimmunity against Sjögren's syndrome. METHODS: We inactivated the genomic ICA69 locus, generated NOD congenic mice that were deficient in ICA69, and assessed development of Sjögren's syndrome. ICA69 autoimmunity was investigated in controls and in patients with primary Sjögren's syndrome or systemic lupus erythematosus, and in various NOD mice, some of which were given an ICA69-directed prototype peptide vaccine. FINDINGS: Disruption of the ICA69 locus prevented lacrimal gland disease and greatly reduced salivary gland disease in NOD mice. In healthy NOD mice, ICA69-specific T cells accumulated in lymph nodes that drain salivary tissue. T-cell and B-cell autoreactivity against ICA69 was much the same in patients with primary Sjögren's syndrome, but not in those with systemic lupus erythematosus or in healthy controls. Immunotherapy with a high-affinity mimicry peptide targeting ICA69-specific T-cells reduced established Sjögren's syndrome in wild-type NOD mice in the long term. INTERPRETATION: ICA69 is a new autoantigen in primary Sjögren's syndrome that has an important role in progression of disease and could be of diagnostic value. Immunotherapy of primary Sjögren's syndrome is promising, since autoimmunity in NOD mice with Sjögren's syndrome seems to be uniquely susceptible to such treatment even late in disease.