Non-Paraneoplastic Autoimmune Retinopathy: The First Case Report in Korea

Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Fullfield electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23-kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea.     

Hepatic centrilobular zonal necrosis with positive antinuclear antibody: a unique subtype or early disease of autoimmune hepatitis?

Centrilobular zonal necrosis (CZN) is not a pattern typically associated with autoimmune hepatitis (AIH). However, it has occasionally been reported that CZN occurs without the classic histologic features of AIH in patients with autoimmune abnormalities. In this study, we examined the clinicopathological features of 5 cases of CZN with autoimmune features not associated with classic AIH. The patients were 1 man and 4 women (24-82 years). Three patients had subjective symptoms (general malaise, arthralgia, and fever). All had antinuclear antibodies (1:40 to 1:1280). Liver biopsy showed CZN without any histologic features of classic AIH. Liver injury was sustained without medication in 4 cases, whereas it was spontaneously improved in 1 case. However, 2 months later, this patient was found to have recurrent liver dysfunction. Liver biopsy at the time of recurrence again showed CZN without the features of classic AIH. All patients were effectively treated with prednisone. Based on a review of a total of 17 cases of CZN with autoimmune features, including previously reported cases, the patients could be classified into 3 groups: cases without recurrence, cases with recurrent CZN, and cases with progression to classic AIH. Patients of the 2 former groups did not develop classic AIH during follow-up. Factors predictive of recurrence were younger age, being male, and high serum bilirubin or transaminase concentrations at first presentation (P < .05). This study suggested that CZN with autoimmune features corresponds to the early stage of classic AIH in some cases and might be a distinct type of autoimmune liver disease in others.     

Circulating anti-retinal antibodies as immune markers in age-related macular degeneration

Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age-matched controls to detect circulating anti-retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age-matched control subjects (n = 39). The sera were analysed for anti-retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93.75%) and CNV (82.27%) were found to have a significantly (P = 0.02) higher titre of autoantibodies to the retina in comparison with controls (8.69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0.0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti-retinal immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD.     

Autoantibody Frequency in Celiac Disease

AIM:

In our study, we investigated the levels of glutamic acid decarboxylase antibody (anti-GAD), islet cell antibody (ICA), thyroperoxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), antinuclear antibodies (FANA), antibodies to double-stranded DNA (anti-ds DNA), antibody to Sjögren syndrome A antigen (anti-SSA), antibody to Sjögren syndrome B antigen (anti-SSB), Smith antibody (anti-Sm), smooth muscle antibodies (ASMA), and antimitochondrial antibody liver-kidney microsome (AMA-LKM) in patients with celiac disease as compared to healthy controls and autoimmune hypothyroid patients.

MATERIALS AND METHODS:

A total of 31 patients with celiac disease, 34 patients with autoimmune hypothyroidism and 29 healthy subjects were included in this study. Anti-SSA, anti-SSB, anti-Sm, anti-ds DNA, anti-GAD, anti-TPO and anti-TG were studied by Enzyme-Linked Immunosorbent Assay (ELISA), and AMA-LKM, ASMA, ANA and ICA were studied by immunofluorescence. Clinical data and the results of free thyroxine-thyroid stimulating hormone (FT4-TSH) were collected from the patients’ files by retrospective analysis. SPSS ver 13.0 was used for data analysis, and the χ² method was used for comparisons within groups.

RESULTS:

The frequency of anti-SSA, anti-SSB, anti-GAD, anti-Sm, anti-ds DNA, AMA-LKM, ASMA, ANA and ICA were not significantly different between the groups. Levels of anti-TPO and anti-TG antibodies were found to be significantly higher (<0.001) in autoimmune hypothyroid patients when compared with other groups.

CONCLUSION:

In previous studies, an increased frequency of autoimmune diseases of other systems has been reported in patients with celiac disease. We found that the frequency of autoimmune antibodies specific for other autoimmune diseases was not higher in celiac disease.     

Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy

Autoantibodies against alpha-enolase are often associated with visual loss in patients with autoimmune retinopathy. Anti-recoverin autoantibodies have been the most extensively studied for their pathologic association with cancer-associated retinopathy (CAR). It has been shown that anti-recoverin antibodies penetrate retinal layers corresponding to the cellular location of recoverin and cause the death of photoreceptors and bipolar cells. However, the pathogenic effects of anti-alpha-enolase antibodies have not been studied. In this study, we tested the labeling and apoptotic effects of such autoantibodies on retinal cells. Serum antibodies against alpha-enolase from patients with autoimmune retinopathy were tested ex vivo and in vivo in Sprague-Dawley rats. Autoantibodies to alpha-enolase specifically labeled the retinal ganglion cells and inner nuclear layer cells. Using ex vivo experiments and intravitreal injections, we observed that antibodies were capable of penetrating retinal tissue to target ganglion cell and inner nuclear layers and, consequently, were able to induce cell death through an apoptotic process. The apoptotic nuclei detected by a DNA fragmentation assay and caspase 3-positive cells were co-localized in the ganglion cell layer and inner nuclear layer. The results showed that antibodies against alpha-enolase target antigens in these layers and induce the apoptotic death of sensitive cells. Rat retinal explants and the intravitreal injection of antibodies provide us with a good model to identify antibody pathogenic targets in the retina. Such identification may help explain the complex of clinical symptoms for autoimmune retinopathy mediated by autoantibody and may help guide treatment strategies.     

Humorale Autoimmunphänomene unter Langzeittherapie mit Lithium unter besonderer Berücksichtigung schilddrüsenspezifischer Autoantikörper

Summary In a retrospective study, 58 outpatients under long-term therapy with lithium were examined with regard to humoral autoantibodies. Fifty-five schizophrenic outpatients under neuroleptic treatment served as controls. We examined antithyroidal antibodies (TAK, MAK), smooth muscle antibodies (SMA), antimitochondrial antibodies (AMA), and antinuclear antibodies (ANA). In the lithium group there was a significant higher prevalence of antithyroidal antibodies (33%) as compared to the control group (9%). Ten patients out of 19 patients with antithyroidal antibodies showed MAK as well as TAK; moreover we found a characteristic pattern: MAKTAK. All lithiumtreated patients were euthyroid. Five patients out of the group with antithyroidal antibodies had goiter, three showed temporarily elevated serum concentrations of basal thyroid-stimulating hormone (TSH). We did not find such elevated levels of TSH in the group of eight patients with goiter but without antithyroidal antibodies. There was neither a correlation between the examined parameters and the lithium serum concentration nor the additional psychotropic medication. Our results indicate a significant higher prevalence of antithyroidal antibodies under long-term therapy with lithium as compared to a psychiatric control group. We do not consider these autoimmune phenomena as relevant pathogenetic factors.

     

Prevalence of autoantibodies to the p53 protein in autoimmune hepatitis

The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group (4%). The clinical features of the anti-p53 seropositive AIH patients were similar to those of the seronegative ones. Thus, the prevalence of p53 autoantibodies in AIH is higher than in other forms of chronic hepatitis, and may be useful in differential diagnosis.     

HLA-DR Allele Frequencies in Mexican Mestizos with Autoimmune Liver Diseases Including Overlap Syndromes

Autoimmune liver diseases are sometimes difficult to differentiate from hepatic overlap syndromes (OS). The objective of this study was to use polymorphic genetic markers to better distinguish clinical heterogeneity in autoimmune liver disease. Since autoimmunity is the result of autoantibody production we studied HLA-DR alleles in 20 patients with autoimmune hepatitis (AIH), 16 with primary biliary cirrhosis (PBC), 10 with OS, and in 99 ethnically matched healthy individuals. Patients with OS had significantly higher alkaline phosphatase and total bilirubin levels than patients with AIH. OS patients had a higher prevalence of positive antinuclear antibodies and a higher AIH score than patients with PBC. Patients with OS also had higher total immunoglobulin levels (IgG isotype) as compared to patients with PBC. We found in PBC patients a higher gene frequency of HLA-DR4 and DR1 as compared to healthy controls (p = 0.03, OR = 2.2 and p = 0.004, OR = 4.3, respectively) and to OS patients (p = 0.01, OR = 6.8, and p = 0.004, OR = 10.0, respectively). On the other hand, the gene frequency of HLADR5 was significantly decreased in the total group of patients as compared to healthy controls suggesting a protective role of this allele for developing autoimmune liver disease.     

Autoantibodies to p75/LEDGF, a cell survival factor, found in patients with atypical retinal degeneration

We have identified a group of patients with an atypical retinal degeneration having anti-retinal autoantibodies in their sera. This select population is characterized by a progressively severe loss of vision associated with a decrease in photoreceptor function, abnormal pigmentation of the retinal pigment epithelium and a negative family history of retinal dystrophy. Immunohistochemical analysis on mouse retinal tissues with sera from this group of patients demonstrated high titers of anti-retinal antibodies (320 to 1,280). Anti-retinal reactivity at these levels was not detected in sera from normal individuals, or from patients with uveitis or known genetic retinal degenerations. One antigen that was identified from a retina cDNA library with sera from a patient with atypical retinal degeneration was lens epithelium-derived growth factor (LEDGF). Western blot analysis revealed that sera from all three patients demonstrated reactivity to p75/LEDGF, a survival factor that protects cells from oxidative, thermal and UV damage. In conclusion, we have found a novel group of patients with a retinal degeneration of non-paraneoplastic, non-familial origin demonstrating immunoreactivity to an autoantigen, p75/LEDGF, heretofore not associated with this disease. Finally, identification of specific anti-retinal antibodies may have applications in the diagnosis and management of retinal degeneration.     

The Hepatitic/Cholestatic "Overlap" Syndrome: An Italian Experience

Background: Patients with hepatitic and cholestatic autoimmune liver disease ("overlap syndrome") represent a diagnostic and therapeutic challenge. Aim: To evaluate the prevalence of the "hepatitic/cholestatic overlap" in a large series of consecutive patients with cholestatic autoimmune liver disease. Methods: We re-evaluated the diagnosis of 235 patients with autoimmune liver disease, including 70 with type 1 autoimmune hepatitis (AIH), 142 with primary biliary cirrhosis (PBC), and 23 with primary sclerosing cholangitis (PSC), using the revised International Autoimmune Hepatitis Group (IAIHG) scoring system. Anti-mitochondrial, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, perinuclear anti-neutrophil nuclear and anti-soluble liver antigen antibodies were evaluated in each patient. Results: Ten patients (3 with a previous diagnosis of PBC and 7 of PSC) scored as "probable" or "definite" AIH. These patients did not have a specific autoantibody profile. Conclusions: Among patients with PBC, the occurrence of a PBC/AIH overlapping syndrome is rare (2.1%), whereas among patients with PSC an overlap between PSC and AIH is frequent (30.4%). Whether patients with the hepatitic/cholestatic overlap syndrome would benefit from a combination therapy with immunosuppression and ursodeoxycholic acid remains to be established.     

Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus.

Diabetes mellitus is associated with vascular and neurological complications. We have investigated the presence of antibodies to phospholipids and to phospholipid binding plasma proteins in blood samples collected from 68 clinically and biochemically characterized type I and type II diabetic patients and from 252 healthy blood donor controls. Each sample was analysed for antibodies to three phospholipids (cardiolipin, phosphatidylserine and phosphatidylethanolamine), the antibody isotypes (IgA, IgG and IgM), and whether antibody activity was plasma protein-dependent. Patients were considered to have anti-phospholipid antibodies when one or more of these 18 tests was found above predetermined control values. The results of these experiments revealed an increased incidence of anti-phospholipid antibodies in diabetic patients compared with control subjects. The incidence of IgA isotype to phosphatidylethanolamine was higher than the incidence of other isotypes to other phospholipids, and their reactivities were independent of phospholipid-associated proteins. In addition, these antibody findings were studied for associations with prothrombin degradation products, activated factor VII and activated protein C, and with the incidence of diabetic complications. The anti-phosphatidylethanolamine antibody association with proliferative retinopathy was significant.     

Prevalence of Autoantibodies to the p53 Protein in Autoimmune Hepatitis

The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group (4%). The clinical features of the anti-p53 seropositive AIH patients were similar to those of the seronegative ones. Thus, the prevalence of p53 autoantibodies in AIH is higher than in other forms of chronic hepatitis, and may be useful in differential diagnosis.     

Autoimmune hepatitis

Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.     

自身免疫性肝炎合并自身免疫性疾病的特征研究

目的 比较自身免疫性肝炎（AIH）合并原发性胆汁性胆管炎（PBC）或部分肝外自身免疫性疾病（autoimmune disease）患者与单纯AIH患者临床特点及并发症,为改善AIH患者的诊治提供参考。方法 收集1999年8月~2019年8月我院收治的AIH患者149例,根据合并症分为无合并病的AIH组（68例）、AIH合并PBC组（AIH-PBC 组,41例）及AIH合并肝外自身免疫性疾病组（AIH-肝外组,40例）,比较三组临床特点、并发症、肝纤维化/肝硬化进展情况。结果 ①AIH-PBC 组及AIH-肝外组年龄低于AIH组,差异有统计学意义（P＜0.05）;三组性别比较,差异无统计学意义（P＞0.05）。②三组共有的临床症状为瘙痒、黄疸、乏力、食欲不振及腹部不适,其中AIH-PBC组瘙痒症状患者多于AIH组、AIH-肝外组,差异有统计学意义（P＜0.05）;三组黄疸、乏力、食欲不振及腹部不适比较,差异无统计学意义（P＞0.05）。③AIH-PBC 组ALT低于AIH组及AIH-肝外组,ALP、GGT高于AIH组及AIH-肝外组,差异有统计学意义（P＜0.05）;AIH-肝外组的AST、DBIL高于AIH组及AIH-PBC 组,差异有统计学意义（P＜0.05）;AIH-肝外组IgG水平高于AIH组及AIH-PBC 组,差异有统计学意义（P＜0.05）。④三组ANA、ASMA、SLA、LKM-1阳性率比较,差异无统计学意义（P＞0.05）;AIH-PBC组AMA、AMA-M2 阳性率高于AIH组、AIH-肝外组,差异有统计学意义（P＜0.05）。⑤三组均以界面性肝炎和淋巴细胞浸润表现居多,其中AIH-PBC组胆管病变、胆汁淤积高于AIH组,差异有统计学意义（P＜0.05）。⑥三组并发症主要包括食管胃底静脉曲张/破裂出血、腹水、肝性脑病、肝癌、肝移植,组间比较,差异无统计学意义（P＞0.05）。⑦三组肝纤维化/肝硬化发生率比较,差异无统计学意义（P＞0.05）;但AIH-PBC组2~5年肝纤维化/肝硬化进展率高于AIH组及AIH-肝外组,差异有统计学意义（P＜0.05）。结论 合并PBC的AIH患者比单纯AIH患者诊断年龄早,肝脏炎症反应轻、胆管病变重;比AIH及合并肝外自身免疫性疾病更易出现瘙痒、胆汁淤积更重、胆管损伤更严重,且肝纤维化/肝硬化速度更快。AMA、AMA-M2可作为AIH合并PBC的鉴别指标。另外,AIH合并肝外自身免疫性疾病常存在肝功能损害,IgG对其具有提示意义。     

育龄妇女不育不孕的实验室诊断及实验结果分析

目的探讨育龄妇女自身免疫抗体及生殖道衣原体(CT)、支原体(UU)感染与不育不孕患者的关系。方法选择2007年来我院门诊就诊和妇科住院的自然流产患者、不孕患者,没有反复流产史,且有一个健康婴儿的健康体检者,分别检测封闭抗体(APLA)、抗精子抗体(AsAb)、抗子宫内膜抗体(EMAb)、抗心磷脂抗体(ACA)解脲支原体(UU)和沙眼衣原体(CT)。结果自然流产患者中APLA阴性占75%,不孕患者APLA阴性占17.73%,对照组APLA阴性占8.14%;流产组、不孕组的APLA、AsAb、EMAb、ACA、UU、CT阳性检出率明显高于对照组。结论育龄妇女体内存在APLA、AsAb、ACA、EMAb及生殖道支原体或衣原体感染与不育不孕患者密切相关,对有不良孕产史及不孕的患者进行自身免疫抗体及生殖道衣原体、支原体的检测,可为诊断及治疗提供科学的依据。     

Physical activity and autoimmune diseases: Get moving and manage the disease

Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance. With the advent of biological therapies, better outcomes have recently been noted in the management of autoimmune diseases. Nonetheless, recent research highlights the salient role of modifiable behaviors such as physical inactivity on various aspects of the immune system and autoimmune diseases. Physical activity leads to a significant elevation in T-regulatory cells, decreased immunoglobulin secretion and produces a shift in the Th1/Th2 balance to a decreased Th1 cell production. Moreover, physical activity has been proven to promote the release of IL-6 from muscles. IL-6 released from muscles functions as a myokine and has been shown to induce an anti-inflammatory response through IL-10 secretion and IL-1β inhibition. Physical activity has been shown to be safe in most of autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel diseases (IBD), as well as others. Additionally, the incidence of RA, MS, IBD and psoriasis has been found to be higher in patients less engaged in physical activity. As a general trend, patients with autoimmune diseases tend to be less physically active as compared to the general population. Physically active RA patients were found to have a milder disease course, better cardiovascular disease (CVD) profile, and improved joint mobility. Physical activity decreases fatigue, enhances mood, cognitive abilities and mobility in patients with MS. In SLE patients, enhanced quality of life and better CVD profile were documented in more physically active patients. Physically active patients with type 1 diabetes mellitus have a decreased risk of autonomic neuropathy and CVD. Both fibromyalgia and systemic sclerosis patients report decreased disease severity, pain, as well as better quality of life with more physical activity. Further, SSc patients improve their grip strength, finger stretching and mouth opening with increased level of exercise. The purpose of this paper is to review the clinical evidence regarding the safety, barriers to engagement, and impact of physical activity on autoimmune diseases.     

Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

INTRODUCTION:

Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis.

METHODS:

One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X‐ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti‐liver/kidney microsomal autoantibodies1, liver‐specific protein, anti‐smooth muscle antibodies, and anti‐mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases.

RESULTS:

The mean age of the patients was 63,13±8,6 years. The mean values of L1‐L4 T‐scores and femur total T‐scores were ‐3,08±0,58 and ‐1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3%) were antinuclear antibodies, four (2.7%) were liver membrane antibodies, three (2.0%) were anti‐liver/kidney microsomal autoantibodies1, and two (1.3%) were liver‐specific protein positive. None of the patients had anti‐mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range.

CONCLUSIONS:

The presence of liver membrane antibodies, liver‐specific protein, and anti‐liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings.     

Bedeutung des arteriellen Blutdruckes für das Auftreten einer Mikroalbuminurie und Retinopathie bei Typ I Diabetes mellitus

Summary The role of hypertension for the combined occurrence of incipient diabetic nephropathy and diabetic retinopathy (RP) was evaluated in 155 insulin-dependent diabetic patients (74 male/81 female); mean age 32.4±12.2 STD years; mean diabetes duration 12.8±10 STD years). Albumin excretion rate (AER) was measured in 24 hours urine samples by RIA, retinal status was determined by both, fundoscopy and fluorescein angiography. Analysis of the data revealed a statistically significant correlation between the duration of disease and elevated AER (p<0.012), and the occurence of retinopathy (p<0.0001). Although there was a close correlation between retinopathy and elevated AER (p<0.0001), it is remarkable that 31% of the patients with normal AER (<15 µg/min) showed signs of non proliferative RP. On the other hand 30% of patients without retinal changes showed an elevated AER (>15 µg/min). In the group of microalbuminuric patients (>15 µg/min) systolic (p<0.004) and diastolic (p<0.04) blood pressures were significantly higher than in normoalbuminuric patients (<15 µg/min). Patients with proliferative retinopathy showed significantly higher systolic and diastolic (p<0.015) blood pressures compared to patients without retinal changes, though albumin excretion rates were not different in both groups of patients. In conclusion, our results show that diabetic nephropathy and diabetic retinopathy do not develop simultaneously in a representative number of insulin-dependent diabetic patients, but hypertension may be a major risk factor for the development of both microangiopathic complications.

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Abkürzungen AER Albuminexkretionsrate - RP diabetische Retinopathie     

Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies

The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.     

Diagnostic features of the autoimmune retinopathies

The term autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that affect retinal function, often but not exclusively at the level of the photoreceptor. They typically present with painless visual loss, which may be accompanied by normal fundus examination. Some are progressive, often rapidly. They present a diagnostic challenge because there are no standardised clinical or laboratory based diagnostic criteria. Included within the spectrum are cancer-associated retinopathy, melanoma-associated retinopathy and presumed non-paraneoplastic autoimmune retinopathy. Differentiation from other retinopathies can be challenging, with overlap in symptoms, signs, and investigation findings, and an absence of pathognomonic features. However, technological developments in ophthalmic imaging and serological investigation over the past decade are adding novel dimensions to the investigation and classification of patients with these rare diseases. This review addresses the clinical, imaging, and serological features of the autoimmune retinopathies, and discusses the relative strengths and limitations of candidate diagnostic features.