Rolf Manthorpe

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

Objective. To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögrens syndrome (SS).

Autoimmune liver disease in patients with primary Sjögren's syndrome

Forty-five patients with primary Sjögrens syndrome were studied for evidence of autoimmune liver disease. Twenty-nine patients had normal liver function tests, normal IgM and a normal test for antimitochondrial antibodies and smooth muscle antibodies. Among the remaining 16 patients, abnormal liver function tests were found in 12 (27% of all patients); eight of these patients had biochemical cholestasis. Elevated plasma IgM (> 2 g/l) was observed in nine patients, three with normal liver function tests, while antimitochondrial antibodies were positive in six patients, one with normal liver function tests, and smooth muscle antibodies were found in three. Based on these findings and percutaneous liver biopsy, a diagnosis of primary biliary cirrhosis was established in four patients and autoimmune chronic active hepatitis in two. The present study showed that abnormal liver function tests in patients with primary Sjögrens syndrome are frequent and may indicate associated autoimmune liver disease. These data further emphasize the systemic nature of autoimmune disorders.

Progress and regression within primary Sjögren's syndrome

The purpose of this review is to give a modern view and an update of important areas in primary Sjögrens syndrome (SS), which may be the most common of the autoimmune systemic rheumatic diseases 1. Interest in aspects of primary SS including clinical manifestations, pathogenesis, aetiology, treatment, prognosis, etc 2 has increased during the past three decades, the volume of scientific papers and the number of theses being the indicators. However, only a fraction of the money that is used for research into rheumatoid arthritis (RA) is used for SS, and the statement that SS is under‐diagnosed, under‐treated and under‐researched 3 will still be valid for several years to come. The topics that are focused on in this review are: (a) clinical areas with subsections on signs and symptoms, terminology, predictors for development of non‐Hodgkin malignant lymphoma (NHML) and prognosis, (b) treatment, (c) the Danger model (aetiopathogenesis) and (d) pathology, including immunoglobulin G4 (IgG4)‐positive cells.

Autotransplantation of cryopreserved ovarian tissue to the right forearm 4(1/2) years after autologous stem cell transplantation.

Premature ovarian failure (POF) may occur as a consequence of chemotherapy and of irradiation to the ovaries (1). Alkylating agents such as cyclophosphamide and chlorambucil are particularly prone to cause ovarian damage (2). The human oocytes are extremely sensitive to radiation. Recently, it was estimated that the radiation required to destroy 50% of the oocytes in human ovaries is less than 2 Grey (3). Besides cryopreservation of embryos and of unfertilized oocytes, cryopreservation of ovarian tissue harvested prior to gonadotoxic treatment is one approach to try to preserve a patient’s fertility. Thus, investigators have reported autotransplantation of fresh ovarian tissue to the forearm (4) and of cryopreserved ovarian tissue heterotopically to the retroperitoneum (5), the rectus abdominis muscle (6) or orthotopically to the remaining ovary (7,8). Recently, Byskov et al. transplanted cryopreserved ovarian tissue to the remaining ovary and could later obtain mature oocytes from the transplant (8). Oktay et al. transplanted cryopreserved ovarian tissue beneath the skin of a woman’s abdomen and succeeded in fertilizing a mature oocyte obtained from the transplant (9). Similarly, Lee et al. obtained mature oocytes from cryopreserved ovarian tissue transplanted to subcutaneous pockets of macaque monkeys. One monkey delivered a healthy female infant at the end of 2003 following in vitro fertilization (IVF) of an oocyte obtained from an abdominal pocket (10). The present report describes the first autotransplantation of cryopreserved ovarian tissue to the forearm of a woman.

Salivary gland involvement in autoimmune thyroiditis, with special reference to the degree of association with Sjo¨gren's syndrome

From a total of 63 patients with autoimmune thyroiditis, 19 cases were further investigated to determine the degree of concomitant morphologic and functional salivary gland changes. For comparison, 21 of a total of 28 cases of primary Sjögrens syndrome were also examined. Of the 19 cases of autoimmune thyroiditis, 11 showed various degrees of salivary gland involvement on the basis of an analysis of lower lip salivary gland biopsy specimens, scintigraphy of the parotid, and unstimulated whole sialometry. Six of these cases fulfilled the criteria of primary Sjögrens syndrome. A remarkably high proportion of dark-staining acini was observed in the lower lip biopsy specimens of our patients with thyroiditis (8 of 19, 42%) and less among our patients with primary Sjögrens syndrome (5 of 21, 24%). We conclude that significant involvement of salivary glands may occur in cases of autoimmune thyroiditis, which indicates that common mechanisms may frequently be operative in the development of thyroid and salivary gland immune disease.

Complement Activation in Patients with Primary Sjogren's Syndrome: An Indicator of Systemic Disease

Sixteen patients with primary Sjögrens syndrome, verified according to the Copenhagen criteria, were investigated for evidence of complement activation. Thirteen of the patients had intact functional activity of both the classical and alternative pathways, with normal concentrations of the complement proteins C1q, C1s, C3, C4 and the complement protein fragments C2a and C3d in the circulation. In contrast, three patients showed clear evidence of complement activation. Further investigation of these patients revealed manifestations of glomerulonephritis, vasculitis and primary biliary cirrhosis. Six months later, one patient developed a malignant non-Hodgkin lymphoma. We conclude that complement activation is generally not associated with primary Sjögrens syndrome. Evidence of complement activation in patients considered to have primary Sjögrens syndrome should raise the suspicion of concomitant systemic disease and/or extraglandular activity.

A reduced level of multiple mutation in a shuttle vector passaged in Sjögen's syndrome cells

Sjögrens syndrome is a systemic disorder with unknown etiology, displaying many signs of autoimmunity. Although the basic mechanism of this disease is unknown, a defect in somatic mutagenesis of antibody genes has been suggested. Using a shuttle vector plasmid, we here show that the number of vectors with multiple base changes in a marker gene was reduced in B cell lines from two patients with Sjögrens syndrome (8% in both), as compared with values reported for cell lines from normal human donors (16-27%). This finding suggests that a reduction of the rate of somatic mutagenesis may influence the development of symptoms in Sjögren patients.

Rose bengal score—A possible key parameter when evaluating disease level and progression in primary Sjögren's syndrome

The rose bengal score is one of the most commonly used tests for evaluation of ocular surface epithelial damage. The test is used in most Sjögrens syndrome criteria. We examined 24 female and four male patients with primary Sjögrens syndrome (primary SS) in order to evaluate possible correlation between the various tests for keratoconjuncivitis sicca (KCS), and for possible correlations to xerostomia and p-IgG levels. Among the KCS tests a high rose bengal score appeared to be the key parameter, being correlated to low break-up time (P less than 0.01), low tear lysozyme (P less than 0.01), appearance of snake-like chromatin in conjunctival imprints (P less than 0.05), low sialometry (P greater than 0.01) and high p-IgG (P less than 0.01). We followed another group of patients with primary SS (30 females and four males) for a mean period of 53 (range 27-76) months. The patients were divided according to their initial response to systemic treatment with bromhexine. KCS parametres and p-IgG were measured repeatedly during the observation period. Patients responding to and continuously treated with bromhexine (2/3 of patients) improved significantly (P less than 0.05) in rose bengal score, but had increasing levels of p-IgG. Non-responders kept their low tear-production rate and had also increasing p-IgG levels. However, when subdivided according to p-IgG level, the group of patients with relatively low p-IgG improved in rose begal score, whereas the high p-IgG-group increased in rose bengal score. The rose bengal score appears to be a useful key parameter when evaluating disease level and progression.

AUTOIMMUNE ANTIBODIES AND PREGNANCY OUTCOME IN WOMEN WITH FALSE-POSITIVE SYPHILIS TEST RESULTS A Retrospective Controlled Investigation of Women from 5170 Deliveries

Nine pregnant women with false-positive syphilis test results, and 13 matched controls, were screened for autoimmune antibodies to ascertain whether any relationship might exist between their presence and the occurrence of obstetric problems. Investigations included assays for anti-cardiolipin antibodies (ACA), lupus anticoagulant (LAC), anti-nuclear antibodies (ANA) (including antibodies against extrac-table nuclear antigen), anti-smooth muscle antibodies, anti-mitochondial antibodies, anti-DNA antibodies, IgM-RF and complement factors. We found no significant difference in the incidence of obstetric problems between the two groups. Exept that significantly more women were positive for ACA in the group with false-positive syphilis tests than in the control group, there were no differences between the groups with regard to the antibodies tested for. There was only one case of SLE, a patient positive for LAC, and who had had several miscarriages and no pregnancy resulting in a live birth. Our findings sugg...

Sjögrens syndrome (SC) ‐ immunological aspects on a generalised disease

SS is diagnosed only by objective methods which should be performed by specialists within ophthalmology and oral medicine & oral surgery. At least two tests within each organ must give abnormal low values. SS is characterised by a general hypofunction of all exocrine glands. Symptoms from other organs are called extraglandular manifestations and are rather common. Not always will there be a good conformity between complaints and objective findings. Consequently tests for lacrimal and salivary gland function are necessary. Various methods exist for determination of lacrimal and salivary gland function. These tests and the consequences of reduced tears on cornea and conjunctive & low amount of salive within the mouth were demonstrated and discussed. The most common and often repeated symptoms in primary SS are universal fatigue and artralgias. Only on the 3rd/4th place the complaints of keratoconjunctivitis sicca and xerostomia occur. The hematological results are within normal limits in most cases, while several serological abnormalities are found. This is mainly due to several occnring autoantibodies. A number of patients have been diagnosed as SLE due to these observations. During the rheumatological/immunological readings there was focussed upon the similar and dissimilaritis between SLE and primary SS.