Immunogenetics of primary Sjögren's syndrome in Colombians

OBJECTIVE: Data concerning the immunogenetic characteristics of primary Sjogren's syndrome (SS) in Latin-Americans are scarce. A research project centered on primary SS in Colombians was initiated in January 1996 to better define these characteristics. METHODS: TAP, HLA, IL-10, and microsatellites on 6p21.3 genotyping was performed by polymerase chain reaction techniques. Immunohistochemistry for Bcl-2 antagonist/killer (Bak) was performed. Autoantibodies and serum level of cytokines (IL-10, TNF-alpha, IFN-gamma, IL-4, and IL-12p70) were determined by enzyme-linked immunosorbent assay. RESULTS: The HLA-DRB1*0301-DQB1*0201 haplotype was associated with disease (OR = 4.3, 95% CI: 1.6 to 11.9, P = 0.002), with a more severe histopathologic picture, and with the presence of anti-Ro and anti-La antibodies. D6S439 microsatellite polymorphism was associated with primary SS in an HLA-independent manner. The most likely gene related to the D6S439 chromosomal location appears to be BAK-1 , which codes for Bak protein, expressed in salivary gland's infiltrate from patients with primary SS but not in controls. IL-10 and IFN-gamma concentrations were significantly higher in patients than in controls ( P < 0.01). IL-10 correlated with titers of IgA rheumatoid factor, anti-Ro, and anti-La antibodies, and with the severity of lymphocytic infiltrate (r > 0.3, P < 0.04). Patients who produced high IL-10 levels had significantly more episodes of cutaneous vasculitis and a higher proportion the IL-10.G9 allele. CONCLUSIONS: The HLA-DRB1*0301-DQB1*0201 haplotype and IL-10 participate in the histopathological progression of SS, autoantibody production, and clinical manifestations. Bak protein and its gene polymorphism may participate in the pathology and susceptibility of disease. HLA and cytokine (IL-10 and IFN-gamma) manipulation may be helpful in treating patients with primary SS.     

The assessment of fatigue in primary Sjögren's syndrome

OBJECTIVE: Disabling fatigue is a prominent feature of primary Sj?gren's syndrome (PSS). We evaluated a number of questionnaires for their ability to discriminate fatigue in PSS from that in other rheumatic disorders and healthy controls. METHODS: 33 female caucasian patients with PSS, 45 with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 30 controls completed self-administered questionnaires including; Visual Analogue Scales (VAS), the Chalder Fatigue Scale (CFS), the Nottingham Health Profile (NHP) and the Medical Outcomes Short Form 36 Questionnaire (SF-36). RESULTS: All patient groups scored significantly worse than controls on the 'Energy' dimension of the NHP, the fatigue VAS and the 'Vitality' domain of the SF-36. No significant differences were observed between PSS patients and controls using the CFS. CONCLUSIONS: The NHP. VAS and SF-36 are useful in identifying fatigue in these rheumatic disorders. Further work is required to identify the characteristic features of fatigue in these conditions.     

Involvement of the peripheral nervous system in primary Sjögren's syndrome

BACKGROUND—Involvement of the peripheral nervous system in patients with primary Sjögren''s syndrome (SS) has been reported, but its prevalence in neurologically asymptomatic patients is not well known.
OBJECTIVE—To assess clinical and neurophysiological features of the peripheral nervous system in patients with primary SS.
PATIENTS AND METHODS—39 (38 female) consecutive patients with primary SS, aged 20-81 years (mean 50), with a disease duration of 1-30 years (mean 8) were studied. The peripheral nervous system was evaluated by a questionnaire, physical examination, quantified sensory neurological examination, and neurophysiological measurements (nerve conduction studies). To assess autonomic cardiovascular function an orthostatic challenge test, a Valsalva manoeuvre, a forced respiration test, and pupillography were done.
RESULTS—Abnormalities as indicated in the questionnaire were found in 8/39 (21%) patients, while an abnormal neurological examination was found in 7/39 (18%) patients. Abnormalities in quantified sensory neurological examination were found in 22/38 (58%) patients. In 9/39 (23%) patients, neurophysiological signs compatible with a sensory polyneuropathy were found. No differences were found in the autonomic test results, disease duration, serological parameters, or erythrocyte sedimentation rate between the patients with primary SS with and those without evidence of peripheral nervous involvement.
CONCLUSION—Subclinical abnormalities of the peripheral nervous system may occur in patients with primary SS selected from a department of rheumatology, but clinically relevant involvement of the peripheral nervous system in this patient group is rare.

     

Nailfold videocapillaroscopy in primary Sjögren's syndrome

Nailfold videocapillaroscopy was performed in 2 groups of subjects: 14 healthy volunteers (C) and 15 patients with primary Sj?gren's syndrome (PSS). This was a controlled clinical trial, matched by age and sex. The aims of this study were to evaluate (1) functional capillary density (number of capillaries with flowing red blood cells per mm(2), FCD); (2) capillary red blood cell velocity at rest (RBV), maximum capillary red blood cell velocity (RBV(max)) after 1 minute ischemia, and the time to reach it (TRBV(max)), taking into account the presence or absence of Raynaud's phenomenon (RP) in the analysis; (3) nailfold capillary morphology; and (4) afferent (AFD), apical (APD), and efferent (EFD) capillary diameters. The mean values obtained for controls versus patients, respectively, were (mean +/- SD): FCD (per mm(2)) 8.0 +/-1.6 and 10.1 +/-3.6; RBV (mm/s) 0.9 +/-0.4 and 0.7 +/-0.2; RBV(max) (mm/s) 1.7 +/-0.9 and 1.3 +/-0.3; TRBV(max) (s) 4.5 +/-0.8 and 5.8 +/-1.6 (p=0.02); and TRBV(max) (s) in patients with RP=6.7 +/-1.6 and without RP=5.6 +/-1.6 (p=0.52). The correlation between RBV and RBV(max) for each group, using the Pearson's coefficient, was significant only for the control group (p=0.007), estimated correlation coefficient = 0.68. Controls and patients showed, in the majority of fields examined, normal morphologic patterns of capillaries. The capillary diameters were AFD (mum) 10.8 +/-1.5 and 11.3 +/-1.8; APD (mum) 16.3 +/-2.4 and 16.8 +/-2.9; and EFD (mum) 12.3 +/-1.4 and 13.7 +/-1.9. These results indicate that these patients have longer time to reach RBV(max), suggesting an impairment of the reactive hyperemia response, which could correlate with clinical features of the disease, ie, abnormal macrovascular and microvascular reactivity.     

Changes in glycosylation of immunoglobulins in primary Sjögren's syndrome

Serum IgG and IgA are glycoprotein and significant glycoform abnormalities have been established in primary Sj?gren's syndrome. The proportion of asialylated IgG is abnormally high in the patients, whereas IgA1 and IgA2 appear to be over-sialylated. This peculiarity might explain the defective binding of IgA to asialoglycoreceptors. Furthermore, the activity of alpha 2,6 sialyl transferase is higher in the IgA-producing B cells from the patients than in the controls, whereas the alpha 2,3 sialyl transferase operates in the former cells but not in the latter. The mechanism of this enzyme dysregulation warrants elucidation.     

A study of the arthritis pattern in primary Sjögren's syndrome

OBJECTIVE: To study the frequency and pattern of arthritis in primary Sj?gren's syndrome (pSS), and its association with clinical and immunological factors. METHODS: 102 patients with pSS diagnosed according to the preliminary European Classification Criteria were examined yearly for 4.5 years in a prospective study design. Arthralgia and arthritis were registered during the 459 patient-years observation period. RESULTS: Arthralgia was reported by 75 patients (73.5%) and arthritis was demonstrated in 18 patients (17.6%) during the observation period. The most commonly affected joints were ancles (n = 7), MCP joints (n = 6), shoulders (n = 6), MTP joints (n = 6) and wrists (n = 5). Symmetrical bilateral arthritis were most commonly observed in ancles (4 patients) and wrists, shoulders and MTP joints. Five patients had longstanding arthritis observed at more than one clinical examination, and one developed seronegative rheumatoid arthritis. Arthralgia/arthritis was not correlated to any clinical or immunological factors, and usually ESR and CRP were normal when arthritis was observed. CONCLUSION: Arthritis in pSS is usually mild, resolving, and unrelated to other clinical and immunological factors. A typical pattern is uni- and bilateral arthritis in the ankles, but joints in hands, feet and shoulders may also be affected.     

Hematologic manifestations of primary Sjögren's syndrome

Sj?gren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized by the mononuclear cell infiltration of exocrine glands exiting in parenchymal damage and secretory impairment. The spectrum of the disease extends from an autoimmune exocrinopathy to a systemic process with extraglandular manifestations. SS is defined as primary (pSS) when isolated, or secondary when associated with another autoimmune disease. Patients with pSS may present hematologic abnormalities, such as anemia, hemocytopenias, monoclonal gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's lymphoma of B-cell origin. The increased prevalence of B-cell malignancies suggests that SS may be a boundary disease between autoimmunity and lymphoproliferation. In this paper, the hematologic manifestations of pSS are reviewed.     

Physical capacity in women with primary Sjögren's syndrome: a controlled study

OBJECTIVE: To examine physical capacity (aerobic capacity, joint mobility, muscle function, and standing balance) in women with primary Sj?gren's syndrome (primary SS) and to examine the correlation of aerobic capacity with fatigue, functional disability, and mental aspects (anxiety and depression). METHODS: Fifty-one women who fulfilled the European Community criteria for primary SS and who had anti-SSA/SSB antibodies or a positive lip biopsy were compared with 51 age-matched controls. Physical capacity, fatigue, functional disability, anxiety, and depression were investigated by means of questionnaires and clinical examinations. RESULTS: The women with primary SS had significantly decreased aerobic capacity (VO(2max) = 28.7 versus 32.4 ml/kg/minute; P = 0.013), shoulder mobility (58 versus 59 scale points; P = 0.003), grip strength (214 versus 259 N; P = 0.000), isokinetic strength of the knee flexors (51 versus 56 Nm; P = 0.049), endurance of the knee flexors (620 versus 712 J; P = 0.008), and standing balance (25 versus 28 seconds; P = 0.006) when compared with the reference group. For the primary SS patients, greater effort was needed to carry out the test of aerobic capacity, and they experienced more pain during the shoulder mobility test. Aerobic capacity correlated with the fatigue experienced (r = -0.33, P = 0.022) but not with functional disability or mental aspects. CONCLUSION: The results indicate that women with primary SS have decreased physical capacity, which may be related to the experience of fatigue.     

Flares of systemic disease in primary Sjögren's syndrome

SIR, Rheumatic disorders such as rheumatoid arthritis (RA) orsystemic lupus erythematosus (SLE) are characterized by a relapsing–remittingcourse, with flares of disease activity [1, 2] amenable to therapy.This has not been well studied for the systemic features ofprimary Sjögren's syndrome (PSS). We report our observationsfrom 59 consecutive patients with PSS, fulfilling the revisedEU–USA criteria [3], who attended a multidisciplinarySjögren's syndrome clinic in Birmingham, UK between 1 January1997 and 31 December 2001. Six further     

Pulmonary manifestations of primary Sjögren's syndrome

Sj?gren's syndrome (SS) is a systemic disease with a predilection for the exocrine glands. It also is considered to be an autoimmune epitheliitis, and, as the respiratory system is lined throughout with epithelial cells, it should not be surprising that patients who have SS may develop pulmonary disease. This article describes these manifestations.     

Nephrocalcinosis: initial manifestation of primary Sjögren's syndrome

INTRODUCTION: Nephrocalcinosis is a rare complication of chronic tubulointerstitial nephritis observed in primary Sj?gren's syndrome. It can precede subjective sicca symptoms. OBSERVATION: We report the case of a 50-year-old woman who presented with a primary Sj?gren's syndrome. The first symptoms appeared 10-years-ago while she was affected with a nephrocalcinosis. CONCLUSION: Autoimmune investigations for Sj?gren's syndrome should be initiated in any patient presenting with nephrocalcinosis and distal renal tubular acidosis.     

Infliximab in primary Sjögren's syndrome: one-year followup

OBJECTIVE: To evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sj?gren's syndrome (SS) over a 1-year period. METHODS: This followup study included 10 of the 16 patients with primary SS who participated in a pilot study. Patients who continued to have symptoms received additional infusions of infliximab for 1 year. RESULTS: All patients completed the 1-year followup for evaluation of efficacy. After 1 year, a statistically significant decrease in global and local disease manifestations was observed in all 10 patients. Treatment was generally well tolerated, with the main side effect being a mild, self-limited infusion reaction. CONCLUSION: Sustained improvement of active primary SS may be possible with infliximab treatment.     

Cardiovascular autonomic dysfunction in primary Sjögren's syndrome

OBJECTIVE: To assess the occurrence and clinical significance of a cardiovascular autonomic nervous system dysfunction in primary Sj?gren's syndrome (pSS). METHODS: Fifty-one pSS patients participated in this case-control study. Heart rate and blood pressure variability measurements, spontaneous baroreflex sensitivity examinations and cardiovascular reflex tests were performed. RESULTS: The results of the heart rate and blood pressure variability measurements and also the baroreflex sensitivity parameters of the pSS patients peaked in the lowest percentile ranges of a database on 559 healthy control subjects (P < 0.05). In three of the five cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05), and the median autonomic neuropathy score was also elevated (3 vs 0 in the controls; P < 0.0001). CONCLUSION: Signs of an autonomic nervous system dysfunction involving the cardiovascular system can be discerned in the majority of pSS patients.     

Sjögren's syndrome in the elderly

Sj?gren's syndrome is an immune exocrinopathy. This paper will deal with the primary Sjogren's syndrome non associated with another rheumatologic disease (polyarthritis or systemic lupus erythematosus). Its prevalence is claimed to increase with age. The main clinical manifestation is salivary and/or ocular dryness due to a lymphocytic infiltration of the salivary or lacrimal glands or both. However, sicca symptoms are very frequent in the elderly, most often iatrogenic. The problem, particularly in this population, is the diagnosis of Sj?gren's syndrome. There are yet no consensual criteria, the most used in the literature are the European criteria, published in 1993 and revised in 1996. Some tests, such as the Schirmer's test and non stimulated salivary flow, are not specific over 60 years. The results of other tests are discussed as the focus score on the lip salivary glands biopsy. The diagnosis of Sj?gren's syndrome should be envisaged in the elderly, when systemic manifestations are associated with sicca symptoms.     

Primary Sjögren's syndrome in the elderly: clinical and immunological characteristics

The objective of the study was to determine the clinical and immunological characteristics of primary Sjogren's syndrome (SS) in patients with an older onset of the disease. We included 223 consecutive patients (204 female and 19 male; mean age at onset 53 years; range 15-87 years) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 31 patients the onset of disease occurred after the age of 70 years, and they represent the elderly-onset group described in this report. The remaining 192 patients presented disease onset before the age of 70 years, and they represent the younger-onset group. Of the 31 (14%) patients with elderly onset of primary SS, 26 were female and 5 male, and the disease onset occurred between 70 and 87 years (mean 74 years). The most common extraglandular manifestations were articular involvement (29%), hepatic involvement (20%), peripheral neuropathy (16%) and interstitial pneumopathy (13%). When compared with patients with a younger onset, the prevalences of glandular and extraglandular manifestations and immunological features (cryoglobulinemia, hypocomplementemia and positivity for RF, anti-Ro/SS-A or anti-La/SS-B) were similar in both groups. In conclusion, although primary SS is typically a disease of middle-aged adults, clinicians should note that it may be diagnosed frequently among elderly patients. However, we could not find any notable differences in clinical and immunological characteristics of patients with elderly onset of primary SS.