Epitopes,immunoglobulin classes and immunoglobulin G subclasses of calsequestrin antibodies in patients with thyroid eye disease

A number of serum autoantibodies are associated with thyroid eye disease (TED), including those reactive against the calcium binding protein calsequestrin (CASQ). There are two isoforms of CASQ namely; CASQ1, found in skeletal, including extra ocular, muscle, and CASQ2, found in cardiac muscle. We determined (i) the reactivity profiles of CASQ1 and CASQ2 antibodies and (ii) the immunoglobulin (Ig) classes and IgG subclasses of CASQ1 antibodies, using enzyme-linked immunosorbent assay. Of the 20 patients with TED tested, 35% were positive for CASQ1 antibodies, 25% for CASQ2 antibodies and two patients (10%) were positive for both antibodies. Of the 12 patients with Hashimoto's thyroiditis and ophthalmopathy tested, 25% were positive for CASQ1 antibodies, 42% for CASQ2 antibodies and two patients (17%) were positive for both antibodies. CASQ1 antibodies were mainly of the IgG class and IgG1 and IgG3 subclasses. These results suggest that CASQ1 and CASQ2 do not share major epitopes. Because antibodies of the IgG1 and IgG3 subclasses are cytotoxic, CASQ1 antibodies may contribute to the eye muscle damage in patients with TED. Because CASQ1 antibodies were positive in only a third of patients with active TED we are unable to draw conclusions about their role in its pathogenesis. On the other hand, a possible role of CASQ2 antibodies in the aetiology of the cardiac complications of Graves' disease is a new avenue for research and appears worthy of further investigation.     

Smoking and disease severity are independent determinants of serum adhesion molecule levels in Graves' ophthalmopathy

Adhesion molecules play a key role in autoimmune disorders, and serum concentrations of soluble adhesion molecules are increased in Graves' ophthalmopathy (GO). Whether this is due to the strong association with smoking is unknown. It is also not known if the severity or activity of GO determine the serum levels of adhesion molecules. We measured serum concentrations of sICAM-1, sVCAM-1 and sELAM-1 in 62 euthyroid Graves' patients with untreated GO, in 62 healthy controls matched for sex, age and smoking habits, and in 26 euthyroid Graves' patients without GO. GO severity was assessed by the Total Eye Score and the activity by the Clinical Activity Score. Adhesion molecules were measured by highly sensitive ELISAs. GO patients had higher levels than controls (median values in ng/ml with range): sICAM-1 300 [171--575] versus 244 [119--674], P < 0.001; sVCAM-1 457 [317--1060] versus 410 [238--562], P < 0.001; and sELAM-1 61 [19--174] versus 53 [23--118], P = 0.021. Euthyroid Graves' disease patients without GO had levels similar to controls: sICAM-1 273 138--453), sVCAM-1 386 [260--1041] and sELAM-1 46 [22--118]. Smoking had an independent effect and was associated with higher levels of sICAM-1 and lower levels of sVCAM-1 in both GO patients and controls; sELAM-1 levels were comparable. In the 62 GO patients, sICAM-1 correlated significantly with severity of eye disease (r = 0.40, P = 0.002). No correlation was found with the duration of GO, the Clinical Activity Score or TBII levels. Multivariate analysis of all 150 subjects showed that the presence of GO and smoking are independent determinants of sICAM-1 and sVCAM-1 concentrations. In GO patients, the Total Eye Score was a stronger determinant than smoking. It is concluded that (i) smoking is associated with increased sICAM-1 and decreased sVCAM-1 levels; (ii) independent from smoking, euthyroid GO patients have higher levels of sICAM-1, sVCAM-1 and sELAM-1 than patients with euthyroid Graves' disease or healthy controls; (iii) the major determinant of sICAM-1 in GO patients is the severity of their eye disease.     

Extraocular muscle autoimmunity and orbital fat inflammation in thyroid-associated ophthalmopathy

The immunological basis for the ophthalmopathy associated with Graves’ hyperthyroidism is both poorly understood and controversial. The mechanism for its link with thyroid autoimmunity is unknown but likely to be due to autoimmunity against some thyroid and orbital tissue-shared antigen, such as the thyroid-stimulating hormone receptor, which is expressed on the orbital pre-adipocyte and extraocular muscle cell, or the putative ‘eye muscle cell membrane antigen’. Chronic upper-eyelid retraction, which sometimes occurs as a dominant feature of ophthalmopathy or as an isolated abnormality, is a common and related orbital disorder. Recent evidence that antibodies targeting the calcium-binding protein calsequestrin are specific and sensitive markers of eye muscle and upper-eyelid muscle damage has highlighted the need for diagnostic antibody tests in ophthalmopathy. In the context of this confusion, this review will address the nature of the autoimmune reactions in thyroid-associated ophthalmopathy, focusing on the eye muscle.     

A 63 kDa skeletal muscle protein associated with eye muscle inflammation in Graves' disease is identified as the calcium binding protein calsequestrin

It is generally accepted that thyroid-associated ophthalmopathy (TAO) is an autoimmune disease of the eye muscle (EM) and the surrounding orbital connective tissue in which circulating antibodies play an important role. Antibodies against EM membrane proteins of 63-67kDa mol. wt. seem to be the best markers of ophthalmopathy in patients with autoimmune thyroid disease. We purified a 63 kDa EM protein using SDS-polyacrylamide gel electrophoresis technology and TAO patients' sera as probes, digested the protein with cyanogen bromide and sequenced immunoreactive peptides. We also screened a human EM library with a rabbit antiserum against 63-65 kDa proteins and affinity purified antibodies from a TAO patient's serum that reacted with a 55 kDa EM membrane protein. From partial sequence information and from DNA sequencing of positive cDNA clones, the protein was identified as calsequestrin, a 63 kDa calcium binding protein localized in the sarcoplasmic reticulum of the muscle fiber. As determined by Northern blotting, calsequestrin was expressed in EM and other skeletal muscle but not thyroid or fibroblasts. Calsequestrin is different from the "64 kDa protein", which has been identified as succinate dehydrogenase flavoprotein subunit, which has a corrected mol. wt. of 67 kDa. Serum antibodies against calsequestrin were found in 40% of patients with clinically active TAO, but in only 4% of those with stable eye disease, and in 5% of normal subjects, by immunoblotting. Although it is possible that autoimmunity against calsequestrin plays a role in the progressive EM damage that characterizes ophthalmopathy it is more likely that the antibodies are secondary to a reaction against some other cell membrane protein, such as the novel thyroid and eye muscle shared protein G2s or the TSH receptor.     

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.

Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in retroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P < 0.0001). In patients with Graves' disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5.5-fold (P < 0.001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.     

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves' disease: the role of CD8+ cells

The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves' disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves' disease.     

Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease

Interleukin 18 (IL-18) is a recently described proinflammatory cytokine. In mouse models it has been shown to play a key role in the development of liver injury. IL-18 binding protein (IL-18BP) is a naturally occurring antagonist of IL-18. In this study we investigated whether IL-18/IL-18BP levels are altered in patients with chronic liver disease (CLD). We measured IL-18 and IL-18BP plasma levels in 153 patients with CLD and 41 healthy controls by a specific ELISA. Plasma levels of IL-18 were significantly higher in CLD patients than in healthy controls. Cirrhotics had higher levels than noncirrhotics. IL-18 levels increased with disease progression. IL-18BP plasma levels paralled the increase of IL-18 with disease progression, except in stage Child C cirrhosis. IL-18 and IL-18BP levels were elevated independent of the etiology of CLD. IL-18 and IL-18BP correlated with laboratory parameters of inflammation and liver injury. Plasma levels of IL-18 and its antagonist, IL-18BP, are elevated in CLD and correlate with severity of disease. IL-18BP may not be sufficient to counteract the overwhelming proinflammatory response in end stage liver disease.     

舌肌肌电图对运动神经元病诊断价值探讨

目的:探讨舌肌肌电图(EMG)对运动神经元病(MND)的诊断价值。方法:对22例 MND患者[其中肌萎缩侧索硬化(ALS)13例,脊肌萎缩症(SMA)9例]进行常规EMG及胸锁乳突肌和舌肌EMG检查,并比较其结果。结果:MND患者EMG舌肌纤颤电位阳性率为59％,而临床表现舌肌纤颤仅32％,EMG敏感性高于临床表现,但经统计学分析差异不明显。ALS与SMA两组常规EMG 比较无明显差异。ALS组舌肌EMG纤颤电位62％(8／13例),胸锁乳突肌纤颤电位39％(5／13例),两者比较差异无统计学意义,但SMA组舌肌纤颤电位阳性率为56％(5／9),胸锁乳突肌EMG无纤颤电位,两者比较差异有统计学意义(P<0.05)。结论:舌肌EMG可作为诊断运动神经元病重要的辅助手段,其诊断价值高于胸锁乳突肌EMG,尤其对SMA病例,与胸锁乳突肌EMG相结合则诊断价值更大。     

87例慢性阻塞性肺疾病患者上下肢肌力等速测试分析

目的　运用等速肌力测试分析慢性阻塞性肺疾病（COPD）患者上、下肢屈、伸肌群的肌力情况。 方法　对87例COPD患者（实验组,其中轻度17例、中度44例、重度26例）和34例健康体检者（对照组）进行肘和膝屈、伸肌群等速肌力测试,分别记录角速度60°/s、180°/s时上、下肢屈、伸肌群的峰力距;计算下肢屈、伸肌群的易疲劳指数。 结果　实验组屈肘肌群和伸肘肌群峰力距分别为（20.56±7.54）N·m、（22.61±9.26）N·m,屈膝肌群和伸膝肌群峰力距分别为（35.78±16.99）N·m、（71.86±27.98）N·m,均低于对照组（P＜0.05）;实验组下肢屈、伸肌群的易疲劳指数低于对照组（P<0.05）。 结论　等速肌力测试可作为分析COPD患者外周肌力变化的一种方法。     

87例慢性阻塞性肺疾病患者上下肢肌力等速测试分析

目的　运用等速肌力测试分析慢性阻塞性肺疾病（COPD）患者上、下肢屈、伸肌群的肌力情况。 方法　对87例COPD患者（实验组,其中轻度17例、中度44例、重度26例）和34例健康体检者（对照组）进行肘和膝屈、伸肌群等速肌力测试,分别记录角速度60°/s、180°/s时上、下肢屈、伸肌群的峰力距;计算下肢屈、伸肌群的易疲劳指数。 结果　实验组屈肘肌群和伸肘肌群峰力距分别为（20.56±7.54）N·m、（22.61±9.26）N·m,屈膝肌群和伸膝肌群峰力距分别为（35.78±16.99）N·m、（71.86±27.98）N·m,均低于对照组（P＜0.05）;实验组下肢屈、伸肌群的易疲劳指数低于对照组（P<0.05）。 结论　等速肌力测试可作为分析COPD患者外周肌力变化的一种方法。     

Expression of T cell receptors alpha beta and gamma delta in the ileal mucosa of patients with Crohn''s disease and with spondylarthropathy.

The expression of the alpha beta and gamma delta heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthropathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the alpha beta + T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the alpha beta + T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The gamma delta + T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that gamma delta T cells are a distinct subset in the intestinal mucosa. The increase in alpha beta + T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease.     

非酒精性脂肪肝患者肝脏固醇调节元件结合蛋白1c的表达及意义

目的 观察非酒精性脂肪性肝病（NAFLD）患者肝组织固醇调节元件结合蛋白（SREBP1c）的表达变化,探讨其在NAFLD病理变化形成中的作用.方法 研究对象为NAFLD患者20例,20例年龄性别匹配的同期住院行肝活检无活动肝病组织学证据且肝脂肪变＜5％的慢性HBV携带者（ASC）设为对照组.免疫组织化学染色检测两组患者肝组织SREBP1c的表达,并比较血脂（TG、CHO）、空腹血糖（FBG）、空腹胰岛素（FINS）和血清肝脏酶谱（AST、ALT、GGT）等的组间差异.结果 与对照组患者比较,NAFLD组肝组织呈不同程度的弥漫性肝细胞脂肪变性,肝组织SREBP1c表达明显升高（P＜0.05）,与此一致,血清ALT、AST、TG、CHO、FBG、FINS水平升高（P均＜0.05）.结论 NAFLD患者肝组织SREBP1 c表达增高,在人NAFLD脂肪变形成过程中起重要作用.     

Expression of mRNA for specific fibroblast growth factors associates with that of the myogenic markers MyoD and proliferating cell nuclear antigen in regenerating and overloaded rat plantaris muscle

Aim: To examine the relations between specific fibroblast growth factors (FGFs) and satellite cell activation during muscle regeneration and hypertrophy in vivo, we measured mRNA expression of FGFs and myogenic markers in rat plantaris muscle after bupivacaine administration and synergist ablation. Methods: mRNA levels for MyoD, myogenin, proliferating cell nuclear antigen (PCNA), p21, M‐cadherin, Pax7, FGF‐1, FGF‐2, FGF‐3, FGF‐4, FGF‐5, FGF‐6, FGF‐7, FGF‐8 and hepatocyte growth factor (HGF) were measured continually for up to 72 h after bupivacaine administration and synergist ablation. FGF‐5, FGF‐7 and HGF proteins were immunostained at 72 h after bupivacaine administration. Results: MyoD and PCNA mRNAs started increasing 24 h after bupivacaine administration. Myogenin, p21, M‐cadherin and Pax7 mRNAs started to increase after 48 and 72 h. After synergist ablation, MyoD, PCNA, M‐cadherin and Pax7 mRNAs had increased at 24 and 48 h, and myogenin and p21 mRNAs at 12 and 24 h. FGF‐1, FGF‐7 and HGF mRNAs after the treatments started to increase at the same time as MyoD and PCNA mRNAs. FGF‐5 was expressed at the same time as MyoD and PCNA mRNAs after bupivacaine administration but did not after the ablation. FGF‐2, FGF‐3, FGF‐4, FGF‐6 and FGF‐8 mRNAs were not associated with the expression of the myogenic markers. FGF‐7 and HGF proteins were expressed in immature muscle fibre nuclei and the extracellular matrix, but FGF‐5 protein was preferentially expressed in extracellular matrix. Conclusion: These results indicate that FGF‐1, FGF‐7 and HGF are associated with specific myogenic marker expression during muscle regeneration and hypertrophy.     

The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series

Graves' disease (GD) and autoimmune thyroiditis (AT) are the two main clinical presentations of AITD, and their clinical hallmarks are thyrotoxicosis and hypothyroidism, respectively. GD, and AT, can be associated with other organ specific, or systemic autoimmune diseases in the same patient. However discordant results have been reported in the literature about the possible associations. Here, we review the association of GD and other autoimmune syndromes. Furthermore, we report the results of our prospective study that investigated the prevalence of other autoimmune disorders in 3209 GD patients (984 with Graves' ophthalmopathy), with respect to 1069 healthy controls, or 1069 patients with AT, or 1069 with multinodular goiter (matched by age, gender, coming from the same area, with a similar iodine intake).On the whole, 16.7% of GD patients had another associated autoimmune disease; and the most frequently observed were: vitiligo (2.6%), chronic autoimmune gastritis (2.4%), rheumatoid arthritis (1.9%), polymyalgia rheumatica (1.3%), multiple sclerosis (0.3%), celiac disease (1.1%), diabetes (type 1) (0.9%), systemic lupus erythematosus and sarcoidosis (<0.1%), Sjogren disease (0.8%). Moreover, 1.5% patients with GD had three associated autoimmune disorders. Interestingly, patients with Graves' ophthalmopathy (GO) had another autoimmmune disorder more frequently (18.9%), with respect to GD patients without GO (15.6%). However the pattern of the associated autoimmune disorders in GD was not significantly different from that observed in AT patients.In conclusion, we suggest GD patients who are still sick, or who develop new unspecific symptoms (even if during an appropriate treatment of hyperthyroidism) should be appropriately screened for the presence of other autoimmune disorders.     

Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas' heart disease

High levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2 beta ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have been measured in sera from patients with chronic Chagas' Heart Disease (cChHD). These antibodies also recognize an epitope on the second extracellular loop of the beta 1-adrenergic receptor, inducing a functional response on cardiomyocytes. The aim of this study was to gain novel insights into the structural basis of this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic receptor antibodies, which are also commonly found in cChHD patients. To address these questions we immunopurified anti-R13 antibodies and studied the structural requirements of epitope recognition. Results showed that the immunopurified antibodies recognized a conformation of R13 in which the third Glu residue was essential for binding, explaining their low affinity for the mammalian homologue (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual variations in epitope recognition in each of the studied patients. The importance of a negatively charged residue at position 3 for the recognition of anti-R13 antibodies was further confirmed by competition experiments using a Ser3-phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13 antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated either the beta 1-adrenergic or the M2-cholinergic receptor, in strict agreement with the functional properties of the IgG fractions from which they derived, demonstrating that the same parasite antigen may generate antibody specificities with different functional properties. This may be a clue to explain the high variability of electrophysiological disturbances found in cChHD.     

Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimer's disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimer's disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.     

Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer

The aim of this multi-center retrospective study was to evaluate the incidence of hyperprogressive disease (HPD) after second-line treatment with pembrolizumab in patients (n = 167) with metastatic non-small-cell lung cancer (NSCLC) whose tumors expressed programmed cell death ligand 1 (PD-L1) in ≥ 1% and to search for hematological and imaging biomarkers associated with its development. Prior to chemotherapy, neutrophil : lymphocyte ratio (NLR1) and platelet : lymphocyte ratio (PLR1), and prior to immunotherapy, NLR2 and PLR2 were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy (PMMA1) and before immunotherapy (PMMA2) (n = 112). Patients with ∆PMMA (1-PMMA2/PMMA1) × 100 ≥ 10% were considered to have sarcopenia (low muscle mass). After treatment with pembrolizumab on the first computerized tomography (CT) scan evaluation, patients were subdivided as follows as: hyperprogressors (HPs), progressors (Ps), non-progressors (NPs) and pseudoprogressors (PPs). HPs had significantly higher ∆PMMA levels, NLR2 and PLR2 than the other patients. Moreover, in multinomial logistic regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a P [odds ratio (OR) = 0·81; 95% confidence interval (CI) = 0·65–0·99; P = 0·047] or an NP (OR = 0·76; 95% CI = 0·62–0·94; P = 0·012) versus an HP. Higher NLRs tended to decrease the likelihood of being a P versus an HP (OR = 0·66; 95% CI = 0·42–1·06; P = 0·09) and significantly decreased the likelihood of being an NP versus an HP (OR = 0·44; 95% CI = 0·28–0·69; P < 0·0001). Our data suggest that a high pre-immunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.     

Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected coronavirus disease 2019 presenting to the hospital

ObjectivesTo assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared with an ELISA and nucleic acid amplification tests (NATs) in individuals with suspected coronavirus disease 2019 (COVID-19).MethodsPatients presenting to a Dutch teaching hospital were eligible between 17 March and 10 April 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group.ResultsIn the pilot analysis, sensitivity characteristics of LFA were heterogeneous, ranging from 2/20 (10%; 95% CI 0%–23%) to 11/20 (55%; 95% CI 33%–77%). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34%–53%) and specificity of 126/129 (98%; 95% CI 95%–100%). Sensitivity increased to 31/52 (60%; 95% CI 46%–73%) in patients with at least 7 days of symptoms, and to 21/33 (64%; 95% CI 47%–80%) in patients with C-reactive protein (CRP) ≥100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52%–72%) and 125/128 (98%; 95% CI 95%–100%) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68%–91%) in patients with at least 7 days of symptoms.ConclusionsThere is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.