miR-146a and miR-155 expression in PBMCs from patients with Sjögren's syndrome.

BACKGROUND: An increasing number of studies have revealed that microRNA (miRNA) contributes to the pathogenesis of autoimmune diseases. The objective of this study is to investigate the miR-146a and miR-155 levels in peripheral mononuclear blood cells from patients with primary Sjögren's syndrome (pSS) who were not receiving medications and to examine the correlations between these miRNA levels and the clinical features of the disease. METHOD: Using real-time polymerase chain reaction analysis of miRNAs, the miR-146a and miR-155 expression levels were assessed in peripheral mononuclear blood cells from 27 patients with pSS and 22 healthy controls, and the relationships between these miRNA levels and the visual analog scale (VAS) scores for dry mouth, dry eyes, and parotid gland swelling were investigated. RESULTS: Compared with the healthy controls, the miR-146a expression level was significantly increased in the patients with pSS (P = 0.0182) and was positively correlated with the VAS scores for parotid swelling (r = 0.4475, P = 0.0192) and dry eyes (r = 0.4051, P = 0.0361). Although the miR-155 expression level was significantly decreased in the patients with pSS (P = 0.0131), the miR-155 expression positively correlated with the VAS score for dry eyes (r = 0.4894, P = 0.0096). CONCLUSION: Our results demonstrated miR-146a overexpression and miR-155 underexpression in the peripheral mononuclear blood cells of the patients with pSS. Furthermore, the expression levels of these miRNAs correlated with the patients' clinical features. Our data suggest that miR-146a and miR-155 might play important roles in the pathogenesis of pSS and that their expression levels may be useful for diagnosing pSS and for predicting disease activity and therapeutic responses.

Do we need new diagnostic criteria for Sjögren's syndrome?

Diagnostic and classification criteria for Sjögren's syndrome (SS) continue to evolve as more is learned about SS and about autoimmune diseases in general. Among diagnostic or classification criteria for SS that are in current use, most include various and variable combinations of results from questions about symptoms and objective tests, many of which are not specific to SS. Given the rapid increase of genetic knowledge about other autoimmune diseases and the potential of finding and testing new biological agents to treat SS, selection of patients who have as uniform a disease process as possible becomes an important goal to better understand and treat this prevalent autoimmune disease. Such is the goal and promise of the latest entry into the SS classification criteria field.

Tear physiology of aqueous deficiency and evaporative dry eye.

PURPOSE: To determine the differences in tear physiology between aqueous deficiency dry eye (ADDE) and evaporative dry eye (EDE), and evaluate their utility in diagnosis. METHODS: Fifty-six dry eye patients were classified into 30 ADDE and 26 EDE according to the recently published Dry Eye Workshop criteria. A range of tear physiology measures comprising of tear evaporation, turnover rate (TTR), distribution, volume and osmolarity, and meibomian gland dropout were measured in these patients. The effectiveness of the tests, singly and in combinations, in differentiating between the dry eye subtypes was evaluated by retrospective allocation into groups and by Receiver Operative Characteristics (ROC) curve analysis. RESULTS: Statistically significant differences were seen for TTR and tear evaporation (with lower values for ADDE) between ADDE and EDE, but no significant differences were seen for tear osmolarity, volume, distribution, and meibomian gland dropout scores. Differentiation of ADDE and EDE by a cut-off value of 11%/min for TTR was found to have a sensitivity of 86%, specificity of 75%, positive predictive value 89%, negative predictive value 69%, and overall accuracy 83%. The area under the curve on the ROC curve was 0.83. For tear evaporation, a cut-off of 60 g/mh was found to have a sensitivity of 77%, specificity of 55%, positive predictive value 38%, negative predictive value 80%, and overall accuracy 58% in subtype differentiation. The area under the curve was 0.59 on the ROC curve. The distribution curve of the evaporation rates for ADDE and EDE, showed an overlap coefficient of 0.76 indicating that tear evaporation is within a similar range in these two dry eye subtypes. CONCLUSIONS: Tear turnover is significantly lower in ADDE than EDE, but there is considerable overlap of tear evaporation between the two dry eye subtypes. Tear osmolarity and turn over tests can be conducted sequentially to effectively diagnose dry eye and its subtypes.

The development and initial validation of the Liverpool sicca index to assess symptoms and dysfunction in patients with primary Sjögren's syndrome.

BACKGROUND: A validated measure to assess sicca-related symptoms in patients with primary Sjögren's syndrome (1 degrees SS) is required for clinical studies. METHODS: A self-administered questionnaire was developed to assess sicca-related symptoms and dysfunction in 1 degrees SS. This was administered to three groups of 40 respondents to measure construct validity: 1 degrees SS patients, non-SS patients reporting xerostomia and a non-patient group. The frequency of scores and the mean score for each question were calculated for each group. Reliability was assessed by test/retest. RESULTS: The measure consisted of 28 items divided into five domains. Scores for questions in domains were generally worse (higher) for 1 degrees SS patients than for patients with xerostomia. The non-patient group reported the best (lowest) scores for all questions. The Kappa statistic for all but four questions was greater than 0.6, suggesting good reliability. CONCLUSION: Questionnaire showed good construct validity and reliability. The Liverpool sicca index needs to be further validated in larger, multicentre studies.

Elevated blood pressure is not related to saliva flow in patients with Sjögren's syndrome.

OBJECTIVE: The purpose of this study was to determine whether systolic and diastolic blood pressures are associated with salivary flow, dry mouth, or dry eye symptoms in patients with primary Sjögren's syndrome as compared with xerostomic control subjects. STUDY DESIGN: One hundred forty consecutive patients seen at the Sjögren's Syndrome Clinic were categorized retrospectively with various classification schemes: (1) subjective dry mouth; (2) subjective dry eye; (3) European criteria; and (4) international criteria. Data collection included age, gender, systolic blood pressure, diastolic blood pressure, salivary flow rate, focus score, Schirmer's test, and laboratory findings, including antinuclear antibodies, anti-SSA, anti-SSB, IgG, IgA, IgM, erythrocyte sedimentation rate, and rheumatoid factor. RESULTS: No meaningful associations of salivary flow rates with systolic or diastolic blood pressures were found in patients with Sjögren's syndrome or in xerostomic control subjects. An inverse correlation was seen between salivary flow and elevated diastolic blood pressure in xerostomic control subjects only. CONCLUSION: Elevated blood pressure was not related to saliva flow in patients with Sjögren's syndrome.

Risk factors for xerophthalmia in the Republic of Kiribati.

OBJECTIVES: To identify risk factors for xerophthalmia in the Republic of Kiribati. DESIGN: Case-control study. SETTING: The Republic of Kiribati. SUBJECTS: 666 xerophthalmic preschool children (cases) and 816 children without xerophthalmia (controls) from a population-based sample of 4619 children who participated in a xerophthalmia prevalence survey. MAIN OUTCOME MEASURES: Clinical signs of xerophthalmia (night blindness, Bitot's spots, corneal xerophthalmia and keratomalacia). RESULTS: Multivariable logistic regression models showed older age [1.35(1.24, 1.47)] [odds ratio (95% confidence interval)]; male sex [1.32(1.05, 1.67)]; recent diarrhea [1.45(1.10, 1.89)]; severe [3.82(2.73, 5.35)], moderate [3.55(2.04, 6.18)], and mild [3.07(2.33, 4.04)] protein-energy malnutrition; current breast-feeding [0.30(0.19, 0.46)]; higher frequency of consumption of carotenoid-containing fruits and vegetables [0.93(0.80, 0.96)]; and the presence of a Foundation for the Peoples of the South Pacific garden project [0.70(0.52, 0.93)] were each independently associated with xerophthalmia. A recent history of measles was associated with corneal xerophthalmia [7.73(1.78, 33.65)]. CONCLUSIONS: These data provide further evidence of the relationship between xerophthalmia and factors that may be amenable to intervention, and suggest that greater availability and consumption of provitamin A carotenoids is associated with decreased risk of xerophthalmia among preschool children.

PIP: In 1989, in the Republic of Kiribati, two teams consisting of an ophthalmologist, a nurse, two field officers, and two village welfare group members conducted a population-based cross-sectional xerophthalmia survey among 4619 children aged 6-72 months living in the northern atolls of South Tarawa, Abaiang, and Butaritari and the southern atolls of Tabiteuea North, Nonouti, and Abemama. The study aimed to identify risk factors for xerophthalmia in Kiribati. Kiribati has among the highest xerophthalmia rates in the world. 666 children had xerophthalmia, while 816 children did not. The multivariable logistic regression (controlling for age and sex) revealed that significant independent risk factors for xerophthalmia were diarrhea (odds ratio [OR] = 1.45) and wasting (OR = 3.07 for mild wasting; OR = 3.55 for moderate wasting; OR = 3.82 for severe wasting). Factors associated with a protective effect against xerophthalmia included breast feeding (OR = 0.3), consumption of foods rich in vitamin A (OR = 0.93), and presence of a garden project of the Foundation for the Peoples of the South Pacific in the village (OR = 0.7). When the researchers controlled for age, sex, breast feeding status, diarrhea, protein-energy malnutrition, frequency of consumption of foods rich in vitamin A, and the presence of a village garden project, the association between measles and corneal xerophthalmia persisted (OR = 7.73). These findings suggest that greater availability and consumption of foods rich in vitamin A reduces the risk of xerophthalmia among preschool children.

Modified classification of xerophthalmia.

"There are many classifications of xerophthalmia in existence. In the present study all these classification have been exhaustively reviewed. Many objections to previous classifications have been raised following experiences with these classifications for over six years. Based on these objections a self explanatory, easy to remember and modified classification has been proposed, which will be of use in wider areas."

Nutritional blindness in Africa.

Nutritional blindness is loss of useful vision resulting from vitamin deficiency. A malnutrition Xerophthalmia means all the ocular manifestations of inadequate metabolism of vitamin A, nutritional blindness being the end result of the most severe cases. The estimated overall prevalence of nutritional blindness in Africa is very low, below the WHO levels of significance, although isolated clusters of locally high prevalence exist, usually in arid, sparsely-populated regions. The peak age group affected is 2-year olds, with most nutritional blindness having its effect before age 6 years. Xerophthalmia may be considered as a serious side effect of protein-energy malnutrition (PEM). When associated with corneal sequelae of xerophthalmia, PEM has an estimated overall mortality of 50%. Intervention programs, therefore, are more appropriately aimed at the broader condition of life-threatening PEM than at the specifically vision-threatening problem of xerophthalmia. Parameters of significant prevalence detection are discussed, and the relative merits of different forms of vitamin A-specific intervention programs are weighed.