Prolactin and Autoimmunity

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p?=?0.03) specifically, pleuritis (33% vs. 17%, p?=?0.02), pericarditis (30% vs. 12%, p?=?0.002), and peritonitis (15% vs. 0.8%, p?=?0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p?=?0.02) and marginally more proteinuria (65.5% vs. 46%, p?=?0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia.     

Abdominal pain in patient with antiphospholipid syndrome—the role of MDCT angiography on visceral blood vessels

Antiphospholipid syndrome (APS) is an autoimmune disease defined by accelerated atherosclerosis, arterial and venous thrombosis, fetal loss, and the presence of antiphospholipid antibodies (aPL) in the serum and which leads to the occurrence of various vascular events. Nonspecific abdominal pain can be one of the symptoms due to changes on visceral blood vessels. The goal of our work is to show the results we obtained in multidetector computed tomography (MDCT) angiography examination of visceral arteries, comparing patients with primary antiphospholipid syndrome (PAPS) and secondary antiphospholipid syndrome (SAPS) with control group. In this study, we analyzed 50 patients with primary PAPS and 50 patients, with secondary SAPS. The results were compared to 50 patients in the control group. The groups were compared in terms of age, gender, and the most common risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. The study was conducted on 64-MDCT, on which we analyzed quantitative and morphological characteristics of the blood vessel lesions. Patients from the control group had statistically significant elevation of cholesterol and triglyceride levels compared to the patients with SAPS and PAPS (p?<?0.001 and p?<?0.05). The results showed that the frequency of changes is statistically (p?<?0.05 and p?<?0.001) more common in patients with PAPS and SAPS than in the control group. Statistically significant difference between the groups was found in superior and inferior mesentery arteries. Analyzing the number of lesions, there was statistically high difference between the patients with one and two lesions than in patients with four or more lesions (p?<?0.001), lower difference compared to the patients with three lesions (p?<?0.01), while there was low, but yet statistically important difference between the patients with three lesions and those with five or more blood vessel lesions (p?<?0.05). Analyzing percentage of diameter stenosis, we established that the lesions in the groups of 0–30% diameter stenosis (DS) and 30–50% DS in patients with PAPS (n?=?42) and SAPS (n?=?44) are more common than in the control group (n?=?18, p?<?0.05). Analyzing the qualitative characteristics of plaques, we established significantly higher frequency of soft tissue and mixed lesions than calcified ones in patients with PAPS and SAPS (p?<?0.001; p?<?0.05). Our study showed that the subclinical manifestation of the changes on visceral arteries is more common in patients with APS. Patients with abdominal pain were those with two or more lesions, and according to our results, majority had PAPS. Because of its safety and accuracy, the method of choice is MDCT angiography in monitoring the progression of disease.     

Clinical features of lung cancer in patients with connective tissue diseases: a 10-year hospital based study

BACKGROUND: Connective tissue diseases (CTD) might be associated with various malignancies, and one of the most frequent is lung cancer (LC). Despite our understanding of pathogenesis, this association remains still unclear. The aim of the present study is to describe the clinical characteristics of patients with CTD who developed LC. METHODS: Of 375 successive patients with CTD followed up to University Hospital between 1995 and 2004, 24 patients were diagnosed with LC: 11 (46%) had systemic sclerosis (SSc), 6 (25%) rheumatoid arthritis (RA), 6 (25%) systemic lupus erythematosus (SLE), and 1 (4%) dermatomyositis. We analyzed LC stage, radiological presentation, histological type, patients' smoking status, method of diagnosis, treatment applied, and disease outcome. RESULTS: Average duration of CTD was 13.95 (range 0-30) years. Non-small cell lung cancer (NSCLC) was significantly more frequent than small-cell lung cancer (SCLC). Among patients with NSCLC, 21 patients (85%) presented with stage III or IV. With regard to treatment, 13% patients underwent surgery, 25% chemotherapy, 4% patients combined chemo- and radiotherapy and 58% patients had only supportive therapy. The median survival was 5 months (range 1-96 months). CONCLUSION: The majority of CTD patients who developed LC were diagnosed at advanced stage and had poor survival. Efforts for early detection of LC in CTD patients' group are warranted.     

Anti-annexin A5 antibodies and 25-hydroxy-cholecalciferol in female patients with primary antiphospholipid syndrome

Clinical Rheumatology - Vascular antiphospholipid syndrome (VAPS) and obstetric (OAPS) are different entities because some patients only develop thrombosis (without recurrent pregnancy losses) and...     

Gene–Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians

Chronic obstructive pulmonary disease (COPD) is a complex disorder influenced by multiple genetic and environmental factors, as well as their interactions. Since elevated oxidative stress and protease activity characterize the pathogenesis of COPD, variants of genes that can affect these processes have been commonly studied in COPD. However, interactions among genes that can influence oxidative stress and protease activity remain poorly investigated in COPD. The aim of this study was to look into the role of functional variants in matrix metalloproteinases (MMPs) 1, 9, and 12 in the occurrence and/or modulation of COPD, and to analyze their interactions with glutathione S-transferases (GSTs) M1, T1, and P1 in the pathogenesis of COPD in Serbians. The MMP1 rs1799750 G > GG, MMP9 rs3918242 C > T, and MMP12 rs2276109 A > G variants were analyzed by direct detection methods. Gene–gene interactions between variants in MMPs and GSTs were assessed using a case-control model. Our results showed association of the MMP1 GG/GG genotype with COPD (p = 0.036, OR = 2.50). Gene–gene interactions between the GSTM1 null and MMP1 GG (p = 0.028, OR = 2.99) and the GSTM1 null and MMP12 AA variants (p = 0.015, OR = 3.82) were found to significantly increase the risk of COPD occurrence. Furthermore, the MMP12 G variant was found to modify the age of COPD onset (p = 0.025, OR = 3.30), while interaction between the GSTM1 null and MMP9 T variants was found to modify the severity of disease (p = 0.019, OR = 4.83). To our best knowledge, this is the first study revealing several gene–gene interactions affecting oxidative stress and protease activity in the pathogenesis of COPD.     

Clinical and Laboratory Features of the Catastrophic Antiphospholipid Syndrome

Catastrophic antiphospholipid syndrome (CAPS, Asherson’s syndrome) is an unusual form of antiphospholipid syndrome (APS) characterized by multi-organ failure and high mortality. Fortunately, CAPS accounts for less than 1% of APS cases. Due to the rarity of the condition, an international registry of CAPS patients was created in 2000 supported by the European Forum on Antiphospholipid Antibodies held in Taormina, Italy at the Tenth International Congress on Antiphospholipid Antibodies. Clinical and laboratory features are the most important in the criteria for the diagnosis of this syndrome and can affect many organ systems. The majority of patients presented with multiple organ involvement at the time of CAPS. The combination of pulmonary, cardiac, and renal involvement was most commonly seen. The organ systems most commonly involved at the onset include the cardiopulmonary system, primarily characterized by dyspnea and respiratory failure, the central nervous system, and the renal system. Laboratory criteria for the classification of CAPS include the presence of antiphospholipid antibodies—LA and/or aCL and/or β₂-GPI antibodies.     

Influenza vaccination of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)

The role of influenza vaccination in patients suffering from autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), has long been a subject of discussion. The risk of exacerbation of the main disease following vaccination is of particular concern, and needs to be carefully evaluated against the risk of disease flares as a result of infections. Our study included 69 SLE patients and 54 RA patients, all in stable condition. We split the groups into two subgroups each: patients in SLE1 (23 patients) and RA1 (23 patients) received the flu vaccine ("Vaxigrip", Aventis Pasteur) in November 2003. Patients in SLE2 (46 patients) and RA2 (31 patients) were not vaccinated. Throughout the following year, we studied parameters of disease activity and the occurrence of viral respiratory and bacterial infections in our patients. The vaccine was well tolerated in all cases. Vaccinated patients had significantly fewer occurrences of infections. Every viral and bacterial infection resulted in the worsening of the main disease. We believe that influenza vaccine is indicated for SLE and RA patients in stable condition. However, this decision must be made on a patient-by-patient basis. We plan to continue our study with the goal of formulating a better protocol for the clinical practice.     

Pulmonary manifestations in antiphospholipid syndrome

Pulmonary manifestations in antiphospholipid syndrome (APS) are relatively rare compared to other clinical signs of this disease. However, pulmonary microthrombosis is among the most frequent arterial complications of APS. Timely diagnosis of pulmonary manifestations is required due both to their severity and to the high mortality rate. The spectrum of pulmonary disorders in patients with antiphospholipid antibodies is sometimes referred to as the "antiphospholipid lung syndrome", and includes thromboembolism of lung arteries, pulmonary hypertension, adult respiratory distress syndrome, intra-alveolar hemorrhages, postpartum syndrome, and others. Timely diagnosis and correct therapy, as well as good patient-doctor collaboration, can result in stabilization of the patient's condition.     

Stress as a trigger of autoimmune disease

The etiology of autoimmune diseases is multifactorial: genetic, environmental, hormonal, and immunological factors are all considered important in their development. Nevertheless, the onset of at least 50% of autoimmune disorders has been attributed to "unknown trigger factors". Physical and psychological stress has been implicated in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of sundry stressors on immune function. Moreover, many retrospective studies found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. Unfortunately, not only does stress cause disease, but the disease itself also causes significant stress in the patients, creating a vicious cycle. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease. It is presumed that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease, by altering or amplifying cytokine production. The treatment of autoimmune disease should thus include stress management and behavioral intervention to prevent stress-related immune imbalance. Different stress reactions should be discussed with autoimmune patients, and obligatory questionnaires about trigger factors should include psychological stress in addition to infection, trauma, and other common triggers.