Paradoxical alteration of acute-phase protein levels in patients with chronic hepatitis C treated with IFN-alpha2b

Previously we observed elevation of the serum concentration of two acute-phase protein (AFP) complement components (C9 and C1-inhibitor) in patients with chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non-responders (NR). In the present study we investigated the effect of high-dose IFN-alpha therapy on serum concentrations of two positive [orosomucoid (OROSO) and C-reactive protein (CRP)] and two negative [transferrin (TF) and fetuin/alpha2HS-glycoprotein (AHSG)] AFP in an outpatient setting. We investigated blood samples of 40 patients with chronic hepatitis C at the onset and at the end of a 3-month treatment with high-dose IFN-alpha2b (5 MIU/day for 6 weeks, followed by 5 MIU t.i.w.) and of 52 healthy individuals. Serum concentrations of OROSO, TF and AHSG were measured by radial immunodiffusion; CRP levels were determined by immunotubridimetry. Compared to controls, patients with chronic hepatitis C had significantly lower OROSO and CRP, and higher AHSG levels. By the end of treatment, OROSO concentration increased in R (P = 0.0054), but not in NR patients. In contrast, TF levels decreased in R (P = 0.0040), but did not change in NR patients. Similarly, in R patients, AHSG levels tended to decrease (P = 0.0942) following IFN-alpha treatment. We conclude that the acute-phase reaction is suppressed in patients with chronic hepatitis C that may be potentially related to the responsiveness to IFN-alpha therapy.     

Successful high-dose low-molecular-weight heparin thromboprophylaxis in pregnant women with antiphospholipid syndrome

INTRODUCTION: Antiphospholipid syndrome is an autoimmune disorder, defined as the association of antiphospholipid antibodies with manifestations of venous or arterial thrombosis or pregnancy loss. Primary antiphospholipid syndrome means that the patients have the same clinical symptoms and laboratory findings but they are not suffering from systemic lupus erythematosus or a closely related autoimmune diseases. Secondary antiphospholipid syndrome occurs in association with autoimmune or other diseases. AIM, METHODS, RESULTS: 31 pregnancies of 10 women are detailed. 22 pregnancies were without thromboembolic prophylaxis and only 2 pregnancies were successful (9.1%). Out of the 9 pregnancies with high dose low-molecular-weight heparin and low dose aspirin thromboprophylaxis throughout pregnancy 8 were successful (88.8%). All the newborns were healthy. In spite of the long-term low-molecular-weight heparin therapy side effects (osteoporosis or heparin-induced thrombocytopenia) were not observed. CONCLUSION: Considering these results high-dose low-molecular-weight heparin and low dose aspirin prophylaxis is recommended for pregnant women with antiphospholipid syndrome throughout pregnancy.     

Antiphospholipid antibodies in acute coronary syndrome

The authors examined the presence of antiphospholipid antibodies in acute coronary syndrome. As their results show the frequency of antibodies against B2-glycoprotein I is significantly higher (14.4%) than the presence of these antibodies in a healthy control group (2%). Occurrence of antibodies against B2-glycoprotein I is much more higher than the occurrence of IgG- or IgM type antibodies against cardiolipin or lupus anticoagulant. CONCLUSIONS: The authors emphasize the possible role of anti-B2-glycoprotein I antibodies in thrombotic process of acute coronary syndrome. The previous ischaemic stroke was significantly more frequent in those patients medical history in whose serums antibodies against B2-glycoprotein I were present, so the presence of this thrombophil factor in acute coronary syndrome points out the importance of secunder antithrombotic prevention.     

A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8 days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.     

Phenotypic diversity of the recurrent p.Val379Leu missense mutation of the TGM1 gene

Autosomal recessive congenital ichthyosis type 1 (ARCI1), a clinically heterogeneous group of keratinization disorders, develops due to mutations in the transglutaminase 1 (TGM1) gene. Here we report a Hungarian pedigree affected by the lamellar ichthyosis clinical form of the ARCI1 phenotype. Direct sequencing revealed two recurrent heterozygous mutations: a splice site (c.877-2A > G) and a missense (c.1135G > C, p.Val379Leu) mutation. This splice site mutation is the most frequently observed in ARCI1 worldwide. The missense mutation is relatively rare and has been reported in only 13 Scandinavian patients. Comparison of the clinical phenotypes of our Hungarian patients and the Scandinavian patients demonstrates great phenotypic diversity associated with the p.Val379Leu genotype.     

Frequency of superscan on bone scintigraphy: A systematic review

Introduction

Bone scintigraphy (BS) is an important tool for detecting bone metastasis. BS with diffuse increased skeletal radioisotope uptake with absent or faint urinary tract and soft tissue activity is defined as a superscan. In this review, we investigate the different etiologies causing superscan and the reported frequency of superscan among different disease entities.

Materials and Methods

The search terms were ‘bone’ AND ‘superscan’ OR ‘superscan’ in the PubMed database from 1980 to November 2020. Eligibility criteria included the following: Peer-reviewed studies containing original data using 99mTc-phosphate-analogue BS reporting a superscan pattern. Unretrievable papers, imaging modalities other than BS or with insufficient information to assess the aetiology were excluded. The abstracts of every paper and full texts of potentially eligible papers were assessed independently by three observers.

Results

Sixty-seven papers were included (48 case reports and 19 cohort studies). Studies conducted in patients with osteomalacia or skeletal fluorosis revealed superscan in all patients. Other benign causes of superscan were hyperparathyroidism and kidney disease. Among papers with malignant cause, prostate cancer was the most common cause, followed by gastric cancer. The frequency of superscans ranged from 1.3% in a cohort of mixed cancer types up to 2.6% in patients with gastric cancer and up to 23% in a cohort of prostate cancer patients.

Conclusion

Superscan is most frequently seen in prostate cancer, but numerous other cancers and metabolic bone diseases can cause superscan, which should be kept in mind when encountering an unexpected superscan on BS.