Usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases

Procalcitonin (PCT), a precursor for calcitonin, has been reported to be elevated in bacterial infection. However, its significance in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, who have treatment with corticosteroid and immunosuppressive drug, is limited. To investigate the usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, we analyzed 28 patients with systemic autoimmune diseases hospitalized because of fever and/or C-reactive protein (CRP) elevation. PCT was measured by the immunochromatography assay. Fourteen patients were considered having bacterial infections and the other 14 patients were considered having disease flare of their systemic autoimmune diseases. Serum CRP levels in the bacterial infection group was higher than that in the systemic autoimmune disease flare group; however, the difference did not reach statistical significance. The positive rate of serum PCT was significantly higher in the bacterial infection group (10/14, 71%) than that in the systemic autoimmune disease flare group (1/14, 7%), although there were 2 cases showing false positive PCT probably due to rheumatoid factor. This study suggested that PCT is useful in the diagnosis of bacterial infection in patients with systemic autoimmune diseases who are treated with corticosteroid and immunosuppressive drug.     

Serum procalcitonin concentrations in transplant patients with acute rejection and bacterial infections.

Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections. PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome. The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response. PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples. Normal serum levels were in the range of 0.08-0.6 ng/ml. Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients. Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods. Good response to antibiotic therapy was associated with a decline in serum PCT concentrations. Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels. Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max. 7 ng/ml). We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation.     

SARS-CoV-2 infection among patients with systemic autoimmune diseases

ObjectivesThis study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population.MethodsIn this cross-sectional study, Tuscan outpatients with systemic autoimmune diseases followed at a tertiary referral centre were telephonically interviewed between April 1st-14th 2020 to collect demographic and clinical data, information on ongoing immunomodulating/immunosuppressive treatments, and on the presence of symptoms suspected of SARS-CoV-2 or of a confirmed infection.Results458 patients were interviewed [74% female, median age 56 years (IQR 43–68)]; 56% of them were receiving corticosteroids, 44% traditional disease-modifying anti-rheumatic drugs (DMARDs), of whom 23% hydroxychloroquine, 5% colchicine, while 41% were on biologic DMARDs (of whom 9% on tocilizumab). Thirteen patients reported symptoms suggesting SARS-CoV-2 infection. Of them, 7 had undergone nasopharyngeal swab and only one was positive and developed severe SARS-CoV-2 complications. Within our cohort, the prevalence of SARS-CoV-2 infection was therefore 0.22% (0.01–1.21%), comparable to that observed in the general population of Tuscany [0.20% (0.20–0.21%), p = .597].ConclusionsPatients with systemic autoimmune diseases do not seem to carry an increased risk of SARS- CoV-2 infection as compared to the general population.     

Celiac disease in North Italian patients with autoimmune thyroid diseases

Background: Patients with autoimmune thyroid diseases (AITDs) are prone to develop other autoimmune manifestations and to display autoimmune polyendocrine syndromes.

An increased prevalence of celiac disease (CD) was demonstrated in adult European and Italian patients with AITDs; conversely, an increased prevalence of AITDs was demonstrated in patients with CD. An IgA deficiency is the most frequent immunodeficiency in humans and, in general, high frequency of this disorder was demonstrated in those with autoimmune diseases.

Aim: To define the prevalence of both CD and IgA deficiency in North Italian patients with AITDs.

Methods: 276 Italian patients with AITD were enrolled (mean age 42.6 years range 12–89, 186 of whom had chronic thyroiditis and 90 had Graves' disease). The tissue transglutaminase autoantibodies of the IgA class (IgA-tTGAbs) were evaluated using an ELISA method in these patients. Furthermore, the serological levels of the IgA were determined.

Results: Five of the patients (1.8%) were affected by previously diagnosed CD and were on a gluten-free diet. Ten out of the remaining 271 patients (3.6%) were found to be positive for celiac-related autoantibodies. All of these patients agreed to undergo endoscopy and duodenal biopsies and silent CD was found in 5 of them but 5 had not histopathological signs of CD.

CD (clinical, silent or latent) was present in 15/276 (5.4%) of the North Italian patients with AITD; this prevalence is significantly higher with respect to the general population (p < 0.00001).

The genetic pattern of the 10 patients with both AITDs and CD was characterized by the presence of DQ2 in 8 patients and DQ8 in 2. An IgA deficiency was present in 2/276 of the patients (0.72%).

Conclusions: CD is significantly increased in patients with thyroid autoimmune disorders for this reason it is important to screen for CD in patients with AITDs.     

自身免疫性肝病患者血清GP73变化特征

目的 明确自身免疫性肝病患者血清GP73的水平特征及可能的临床意义.方法 本研究共观察了健康体检、慢性乙型肝炎患者,以及自身免疫性肝病患者各80例的血清GP73水平.结果 与健康对照人群的血清GP73水平（35.84±11.8） ng/ml相比,自身免疫性肝病患者（112.3±72.55） ng/ml显著升高,也显著高于慢性乙型肝炎患者（86.44±60.69） ng/ml.但自身免疫性肝炎（107.4±90.6）ng/ml,原发性胆汁淤积性肝硬化（89.0±45.38） ng/ml,以及原发性硬化性胆管炎（113.3±50.87） ng/ml患者之间并无显著性差异,但均低于重叠综合症的患者（153.3±86.89ng/ml）.以健康体检人群为参照人群,以61.35 ng/ml为cut-off值,GP73诊断自身免疫性肝病的特异性和敏感性分别为75.0％和97.53％.ROC分析曲线下面积为为0.93（95％ CI：0.89-0.97）.结论 自身免疫性肝病患者血清GP73显著高于健康对照人群,尤其是那些重叠综合征的患者.对于GP73升高的患者,除考虑病毒性肝炎,肝癌外,也应该考虑自身性免疫性肝病的可能.     

Serum CXCL10 levels and neuromuscular manifestations in patients with autoimmune thyroid diseases

Objective: Serum C-X-C motif chemokine 10 (CXCL10) levels have been shown to be elevated in autoimmune thyroid diseases (AITD). This study sought to determine whether newly diagnosed AITD patients with neuromuscular findings had higher levels of CXCL10 than those without neuromuscular manifestations.

Design: A total of 80 patients were recruited to the study, which included treatment-naive hypothyroid Hashimoto's thyroiditis (n = 19) and hyperthyroid Graves' disease (GD; n = 21), euthyroid thyroid autoantibody-positive (n = 20) and -negative (n = 20) patients.

Methods: All patients underwent a thorough sensorimotor and neuromuscular examination. Serum samples were kept in ? 20°C for further CXCL10 measurements with ELISA.

Results: There was a significant difference with regard to serum CXCL10 levels only between GD and euthyroid thyroid autoantibody-negative patient groups [187(12-418) vs. 37.5(2-542) pg/ml, p < 0.05]. However, a comparison of newly diagnosed AITD patients with and without neuromuscular manifestations in terms of serum CXCL10 levels yielded no significant difference. When a correlation of existence of a neuromuscular manifestation and serum CXCL10 levels was evaluated, a significantly positive correlation was noted between carpal tunnel syndrome (CTS) and serum CXCL10 levels [207 (95-748) pg/ml in CTS-positive vs. 117 (2-977) pg/ml in CTS-negative patients, p < 0.05].

Conclusions: In this study, from a number of neuromuscular manifestations, only the existence of CTS correlated with significantly higher CXCL10 levels in the whole study group. Further studies with larger numbers of patients with autoimmune-based hyper- and hypothyroidism may better clarify the hypothesis regarding a relationship between serum CXCL10 levels and neuromuscular manifestations of AITD.     

Menopause in patients with autoimmune diseases

Menopause represents a time of significant clinical and hormonal change. Given the incompletely understood interrelationship between gonadal hormones and the immune system, it is possible that menopause may affect, or be affected by, the presence of autoimmune disease. Menopause has significant effects on a number of organ systems including the cardiovascular, skeletal, central nervous and genitourinary systems. Premature ovarian failure is related to autoimmune factors in a proportion of cases, but is not generally associated with systemic autoimmune disorders unless secondary to treatment with alkylating agents such as cyclophosphamide. Gonadal hormones have been suggested to relate to both onset and activity in certain autoimmune diseases. For patients with systemic lupus erythematosus, disease activity is lower, and damage accrual higher, in the postmenopausal years, but the mechanisms responsible may relate to age, duration of disease, menopause changes, long-term effects of therapy, or some combination of these factors. Early menopause is a risk factor for rheumatoid arthritis, and post-menopausal status in RA is associated with greater damage and disability. Systemic sclerosis and giant cell arteritis may also be adversely affected by onset of menopause. Importantly, autoimmune disease and menopause may have an additive effect on risk for common comorbidities such as cardiovascular disease and osteoporosis.     

Refractory disease in autoimmune diseases

Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.     

Cyclosporin-associated nephropathy in patients with autoimmune diseases

Summary Renal biopsy specimens were evaluated from patients with different autoimmune diseases treated with cyclosporin (CyA). Ten biopsies were done before CyA, 10 biopsies after low-dose (<7.5 mg/kg/day, initial dose or mean daily dose within the first month, respectively), and 9 after high-dose (>7.5 mg/kg/day) treatment. Definite chronic CyA nephrotoxicity (cyclosporin-associated arteriolopathy and/or interstitial fibrosis striped form with tubular atrophy) was only present in the initial high-dose group. In this group a significant serum creatinine increase was noted and 8 of the 9 patients were hypertensive. No significant correlation was found between the severity of morphologic lesions and the mean daily dose during total treatment, cumulative dose, and duration of therapy. The morphologic changes in the low-dose group did not differ from the control biopsy specimens before CyA treatment. Based on these results, it can be concluded that major nephrotoxicity can be avoided by initial low CyA doses.Abbreviations CyA Cyclosporin A - NSAID Nonsteroidal antiinflammatory drugs - SLE Systemic lupus erythematosus     

Antibodies against Ku protein in sera from patients with autoimmune diseases

Immunoaffinity-purified Ku protein was used to screen sera from patients with systemic lupus erythematosus (SLE), scleroderma, myositis and Sjögren''s syndrome for anti-Ku antibodies in a quantitative immunoblot assay. Sixteen percent of the 159 studied sera were reactive with the Ku protein; significantly increased frequencies of anti-Ku antibodies were found in SLE (19%) and scleroderma (14%) sera. Patients with myositis and Sjögren''s syndrome showed similar frequencies. All positive sera had antibodies to the 86 kD subunit of Ku protein; only one serum did not react with 70 kD subunit. Frequencies of other autoantibodies were compared in anti-Ku positive and negative patients. Only anti-Sm antibodies, especially in the absence of anti-nRNP, appear to be associated with the presence of anti-Ku antibodies. A strong correlation between anti-Ku antibodies and the class II HLA antigen DQw1 (89% of the positive sera) was observed, suggesting participation of MHC genes in the mounting of the anti-Ku immune response.     

利用降钙素原判断细菌感染的临床符合性分析

目的通过实验室数据和临床综合诊断分析血清降钙素原（PCT）在判断细菌感染中的临床符合性。方法对诊断感染的常规指标C反应蛋白（CRP）、白细胞计数（WBC）、中性粒细胞比例（N％）和细菌培养与PCT进行判断感染的临床符合性分析,再对PCT与临床综合诊断结论进行统计学分析来判断感染和非感染,以及不同部位感染的差异。结果当PCT大于0．5ng／ml时与常规指标的符合性大于92％,而且随着PCT的增大符合性进一步增加;PCT与常规指标之间除CRP外均差异有统计学意义（P〈0．01）;PCT的ROC曲线下面积大于全部常规指标;细菌感染与非感染组间PCT差异有统计学意义（P〈0．01）,但对肿瘤合并感染情况较难判断;PCT全身感染与局部感染之间除伤口感染外均差异有统计学意义（P〈0．01）,但在不同部位间差异无统计学意义。结论PCT与临床广泛应用判断感染的常规指标具有较好的吻合性,PCT在判断细菌感染方面选各医院适用的CUTOFF值能起到很好的作用,可以替代常规指标。     

Clinical implications of procalcitonin in Kawasaki disease: a useful candidate for differentiating from sepsis and evaluating IVIG responsiveness

Clinical and Experimental Medicine - Kawasaki disease (KD) is an acute systemic vasculitis and suspected to be triggered by several potential infections in which procalcitonin (PCT) experiences an...     

21-hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison's disease

The diagnostic specificity of recombinant 21-hydroxylase autoantibodies (21OH-Ab) for Addison's disease was tested in adult patients with either Graves' disease (GD), insulin-dependent diabetes mellitus (IDDM), or polyendocrinopathy, as well as in healthy controls. Using a radiobinding assay with in vitro translated recombinant human 21-hydroxylase, we found 21OH-Ab in 24/28 (86%) idiopathic Addison patients, and using an immunofluorescence assay we found adrenal cortex autoantibodies (ACA) in 12/28 (43%) patients (P =0.002). All the 12 ACA-positive sera were also positive for 21OH-Ab and ACA were found in 11/15 (73%) patients with less than 15 years and in 1/13 (8%) patients with 15–38 years of disease duration (P = 0.002). 21OH-Ab were present in 3/92 (3%) patients with GD, in 1/180 (0.6%) with IDDM and in 0/106 healthy subjects. The 21OH-Ab-positive GD and IDDM patients were also positive for ACA. None of 17 patients with polyendocrinopathy, but without Addison's disease, had 21OH-Ab. None of the 180 Belgian IDDM patients had Addison's disease or developed an adrenal insufficiency at follow up. In two out of three Graves patients, the presence of 21OH-Ab was associated with clinical and biochemical signs of adrenal insufficiency. Of the 89 21OH-Ab-negative patients with GD none had Addison’s disease at the time of blood sampling, and 79 were followed up for 5.6–7.5 years and none developed clinical signs of adrenal insufficiency. We conclude that the presence of 21OH-Ab in patients with endocrine autoimmune diseases is highly specific for Addison's disease.     

Cardiovascular disease in autoimmune rheumatic diseases

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis.     

Antibodies against sulphatide in sera from patients with autoimmune rheumatic diseases.

We tested sera of patients with various autoimmune rheumatic diseases for the presence of antibodies against sulphatide (an acidic glycosphingolipid), identified as a target antigen for antibodies against the liver cell membrane. Thirty-five percent (7/20) of patients with lupus in the active stage possessed anti-sulphatide antibodies, whereas 10% (2/20) of those in the inactive stage and 20% (4/20) of those in the stationary stage possessed such antibodies. Moreover, 10% (3/29) of patients with other autoimmune rheumatic diseases also possessed anti-sulphatide antibodies. The level of anti-sulphatide antibodies was significantly correlated with the levels of anti-double-stranded (ds) DNA antibodies (r = 0.634, P less than 0.001) and dextran sulphate-binding IgG (r = 0.407, P less than 0.001). The serum levels of antibodies against sulphatide were correlated with a history of seizures or psychosis in patients with autoimmune rheumatic diseases. Gels coupled with polyanionic dextran sulphate, monoanionic sulphanilic acid and DNA were shown effectively to adsorb anti-sulphatide antibodies in the sera of patients with active systemic lupus erythematosus (SLE) and autoimmune chronic active hepatitis (AI-CAH). These results suggest that the observed reactivity with sulphatide is due to the presence of antibodies capable of reacting with various anionic molecules in the sera of patients with autoimmune rheumatic diseases as well as those with AI-CAH.