IgG Ratio Research Articles

Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: Risk factors and management

Antiphospholipid syndrome (APS) may cause chronic thromboembolic pulmonary hypertension (CTEPH). Current knowledge regarding prevalence and risk factors for CTEPH among APS patients is limited. We sought to determine clinical features and biomarkers that could identify APS subjects suffering from CTEPH, and describe the prevalence, course and treatment outcomes of patients with APS-CTEPH. 504 APS patients were treated in our center during 2008 to 2019. We studied clinical and laboratory features of 69 APS patients, comparing 19 patients diagnosed with CTEPH (APS-CTEPH) and treated accordingly, with 50 consecutive age and gender matched patients with no evidence of pulmonary hypertension (APS-No-CTEPH). CTEPH prevalence was 3.8% in our APS cohort and was linked with the following parameters: primary APS (p < 0.05); prior pulmonary embolism (p < 0.001); recurrent venous thromboembolism (VTE) (p < 0.001); lower platelet counts (p < 0.001); triple anti-phospholipid antibodies positivity (p < 0.001), higher titers of anti-cardiolipin IgG (p < 0.001), anti-B2GPI IgG (p < 0.001), and high Russell viper venom time ratio (RVVT-ratio) (p < 0.05). Additionally, history of catastrophic APS was more prevalent in APS-CTEPH vs APS-No-CTEPH (p < 0.05). Of APS-CTEPH patients, 15/19 underwent pulmonary endarterectomy (PEA): In 12/15 the procedure was elective and resulted in good perioperative and long-term outcomes, while only 1 of 3 patients that underwent urgent PEA survived. CTEPH is relatively common in APS. Primary APS, prior PE, recurrent VTE, thrombocytopenia and specific anti-phospholipid antibodies predict CTEPH in APS. Active assessment for CTEPH in APS patients should be considered, as PEA was found to be effective and relatively safe, especially if electively performed.

PSXII-22 Relationship between beef cow fertility and maternal immunity

Abstract Immunity plays important role in reproduction. There is evidence that maternal immunity changes from a type 1 to a type 2-biased during pregnancy and lack of such a shift may contribute to unsuccessful pregnancy in animals. The objective of the study was to examine the relationship between relative balance between type 1 and type 2 and fertility in suckled beef cows by characterizing relative quantity ratio of IgG 1 and 2 subclasses (IgG1/IgG2). Angus-Hereford cows (n = 394) were synchronized (d0) with a 5-d CIDR protocol. Estrous behavior was monitored using estrus detection aids and visual observation from d5 until AI (d8). On d8 all cows were inseminated at a fixed time and blood samples were collected form to be examined for type1/type/2 ratio and progesterone (P4). A new rapid blood test (D2Dx) was used to assess the type 1/type 2 immunity balance by measuring the relative quantity ratio of IgG1 and IgG2. Pregnancy was determined by ultrasound 48 to 63 days after AI. Overall pregnancy per AI was 51%. Mean relative quantity of IgG1/IgG2 was different (P &amp;lt; 0.05) between non-pregnant and pregnant cows. There was negative relationship between relative IgG/IgG2 ratio and probability of pregnancy to AI (P &amp;lt; 0.05). As IgG1/IgG2 ratio increased, probability of P/AI decreased. Mean relative IgG1/IgG2 ratio was lesser (P &amp;lt; 0.05) in cows detected in estrus vs non-estural cows. There was no correlation between serum P4 concentrations and IgG1/IgG2 ratio. The results indicate that blood IgG1/IgG2 at the time AI has a potential to be used as a marker for pregnancy prediction in beef cows.

Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test.

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)-based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 227 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity

SummaryIn humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother’s strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity.

Multipl miyelomun ABO kan grupları ile ilişkisi

Aim: Multiple myeloma is a heterogeneous, incurable haematological cancer that occurs as a result of the clonal proliferation of plasma cells. The impact of blood groups on human diseases and/or their role in the prognosis of the disease has attracted the attention of scientists since the discovery of blood groups. We investigated the blood group distribution of multiple myeloma patients and whether their blood groups are related to immunoglobulin type.&#x0D; Materials and Methods: 75 multiple myeloma patients and 73128 control group were included in the study, which was planned retrospectively. The statistical evaluation was performed by using Statistical Package for Social Sciences (SPSS) software for Windows 20 (IBM SPSS Inc., Chicago, IL). The normal distribution of the data was evaluated with the Kolmogorov-Smirnov test.&#x0D; Results: In multiple myeloma patients, the rate of A and B blood groups was low, and the rate of O and AB blood groups was high. Heavy chain IgA ratio was higher in B blood group compared to other blood groups. On the other hand, IgG ratio was found higher in O blood group compared to other blood groups.&#x0D; Conclusion: A relationship has been found between immunoglobulin type and blood types in multiple myeloma. More comprehensive studies are needed on this subject.

Increased vulnerability to SARS-CoV-2 infection among indigenous people living in the urban area of Manaus

The COVID-19 pandemic threatens indigenous peoples living in suburban areas of large Brazilian cities and has thus far intensified their pre-existing socio-economic inequalities. We evaluated the epidemiological situation of SARS-CoV-2 infection among residents of the biggest urban multiethnic indigenous community of the Amazonas state, Brazil. Blood samples of 280 indigenous people living in the surrounding area of Manaus were tested for the presence of anti-SARS-CoV-2 IgA or IgG antibodies. The risk factors and sociodemographic information were assessed through an epidemiological questionnaire. We found a total positivity rate of 64.64% (95% CI 59.01–70.28) for SARS-CoV-2 infection. IgA and IgG were detected in 55.71% (95% CI 49.89–61.54) and 60.71% (95% CI 54.98–66.45) of the individuals, respectively. Over 80% of positive individuals were positive for both IgA and IgG.No significant difference in positivity rates between genders or age groups was observed. Moreover, the age group ≥ 60 years old showed the highest antibody ratios (IgA mean ratio = 3.080 ± 1.623; IgG mean ratio = 4.221 ± 1.832), while the age groups 13–19 and 20–29 showed the lowest IgA (mean ratio = 2.268 ± 0.919) and IgG ratios (mean ratio = 2.207 ± 1.246), respectively. Individuals leaving the home more frequently were at higher risk of infection (Odds ratio (OD) 2.61; 95% CI 1.00–1.49; p = 0.048). Five or more individuals per household increased fivefold the risk of virus transmission (OR 2.56; 95% CI 1.09–6.01; p = 0.019). The disproportionate dissemination of SARS-CoV-2 infection observed among the study population might be driven by typical cultural behavior and socioeconomic inequalities. Despite the pandemic threat, this population is not being targeted by public policies and appears to be chronically invisible to the Brazilian authorities.

Immunoglobulin G4-related disease and idiopathic multicentric Castleman's disease: confusable immune-mediated disorders.

IgG4-related disease (IgG4-RD) and idiopathic multicentric Castleman's disease (iMCD) are both rare systemic immune-mediated disorders. However, the pathogenesis differs markedly between the two diseases and differing therapeutic strategies are adopted: IgG4-RD is treated using a moderate dose of glucocorticoids or rituximab, while iMCD therapy involves an IL-6-targeted approach. Nonetheless, some clinical features of IgG4-RD and iMCD overlap, so differential diagnosis is sometimes difficult, even though the classification and diagnostic criteria of the diseases require careful exclusion of the other. The key findings in IgG4-RD are high IgG4:IgG ratio, allergic features and germinal centre expansion involving T follicular helper cells, while iMCD involves polyclonal antibody production (high IgA and IgM levels), sheet-like mature plasma cell proliferation and inflammatory features driven by IL-6. The distribution of organ involvement also provides important clues in both diseases. Particular attention should be given to differential diagnosis using combined clinical and/or pathological findings, because single features cannot distinguish IgG4-RD from iMCD. In the present review, we discuss the similarities and differences between IgG4-RD and iMCD, as well as how to distinguish the two diseases.

Fibrohistiocytic Variant of Hepatic Pseudotumor: An Antibiotic Responsive Tumefactive Lesion.

Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.

Placental response to maternal SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.

Pre-Existing Infant Antibody-Dependent Cellular Cytotoxicity Associates with Reduced HIV-1 Acquisition and Lower Morbidity

SummaryIn humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. We evaluated antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1 exposed uninfected as compared to HIV-1 exposed infected infants had higher ADCC and a combination of ADCC and nAb responses against their corresponding mother’s strains. ADCC did not correlate with nAbs suggesting they are independent activities. The infected infants with high as compared to low ADCC, but not those with higher ADCC plus nAbs, had lower morbidity and mortality up to 1 year after birth. ADCC was lower in BM supernatants as compared to BM isolated IgG, but was not significantly different in the transmitting versus non-transmitting mothers’ BM or plasma. A high IgA to IgG ratio, as in BM supernatants, was also more prevalent in the infected infants, and it was also associated with lower infant ADCC. Overall, ADCC, more so than nAbs, against the exposure strains associates with lower mother-to-child-transmission (MTCT) and decreased post-infection infant morbidity. Future strategies should aim to elicit robust ADCC activity to prevent MTCT and to improve infant outcomes.

Establishment and application of an immunoassay for the simultaneous detection of IgG and its subtype IgG4 autoantibodies against M-type phospholipase A2 receptor

BackgroundThe renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed. MethodsWe established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls. ResultsThe sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %. ConclusionsThe dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.

IgG4-related orbital disease

A 67-year-old man presented with a 3-week history of diplopia and left ocular pain. Examination showed limitation of abduction of the left eye. Computed tomographic scan demonstrated a soft tissue density mass in the ethmoid sinus (yellow arrow) with extension into the left orbit and infiltration of the medial rectus muscle (Fig. 1A). Incisional biopsy revealed a dense lymphoplasmacytic infiltrate (Fig. 1B), storiform fibrosis, and obliterative phlebitis (yellow arrow, Fig. 1C). Immunohistochemistry was positive for immunoglobulin 4 (IgG4; IgG4+ cells > 30/hpf and IgG4:IgG ratio > 40%) (Fig.

IgG4-related liver disease, presenting as a liver tumour (a case report and review of literature)

IgG4-related disease is a multisystemic fibroinflammatory condition, although the liver involvement by the disease is rare. The disease is characterised by distinctive histopathologic features, most notably dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. The diagnosis should be made only by an interdisciplinary approach to correlate clinical history, pathological picture and radiological findings. We report a case of an 80-year-old male patient presenting with a left lower lobe liver mass. An intrahepatic cholangiocarcinoma was suspected on imaging studies. The patient underwent left hemi-hepatectomy. Macroscopically there was a poorly circumscribed firm tumour measuring up to 47 mm, present within liver parenchyma. Microscopic examination showed dense hyalinised fibrotic hypocellular tissue with fibroblastic proliferation admixed with lymphoplasmacytic infiltrate with focal formation of lymphoid follicles. The entire lesion was then submitted and no malignancy was detected. IgG and IgG4 immunohistochemical stains demonstrated an increase in number of IgG4 positive cells (more than 30 per high power field), as well as an increase in the ratio of IgG4 to IgG positive plasma cells. This immunophenotype is in keeping with IgG4-related liver disease.

Correlation between antibody response against porcine epidemic diarrhea virus in sows and their offspring under field conditions.

Background and Aim:Thai pig farmers have suffered huge financial losses from porcine epidemic diarrhea (PED) since 2007. PED, caused by the PED virus (PEDV), leads to severe diarrhea, vomiting, and subsequent dehydration in suckling piglets. Lactogenic immunity derived from colostrum and milk is very important because immunoglobulins (Ig) cannot cross the placenta in pregnant sows. The aim of this study was to investigate the immunological correlation of the sample-to-positive (S/P) ratios of IgA and IgG against PEDV between colostrum, sow serum, and their piglet serum.Materials and Methods:A total of 43 sows were divided into three groups according to the experience of PEDV infection: Negative sow group (n=7) and treatment group (n=36, sows previously infected with PEDV). The treatment group was subdivided into two groups: Sows immunized with live-attenuated PEDV vaccine (n=15) and sows immunized with feedback (n=21) at 3 weeks before farrowing. The 7-day-old piglets (n=425) were obtained from negative sows (n=89), vaccinated sows (n=150), and feedback sows (n=275). Colostrum, sow serum, and their piglet serum were collected and analyzed for S/P ratios of their IgA and IgG levels against PEDV using an enzyme-linked immunosorbent assay.Results:The piglets from sows immunized with live-attenuated PEDV vaccine had a higher S/P ratio of IgG against PEDV (p<0.001), whereas the piglets from the feedback group had a higher S/P ratio of IgA against PEDV (p<0.001) compared with piglets from the negative sows. In addition, the S/P ratios of PEDV-specific IgA and IgG between sow serum and colostrum showed a positive correlation (Pearson’s coefficient r=0.61 and 0.75, respectively). Both S/P ratios of PEDV-specific IgA and IgG in sow serum and colostrum had a positive correlation to those in piglet serum.Conclusion:Overall, this study suggested that pregnant sows immunized with the live-attenuated vaccine against PEDV and feedback may provide maternal immunity against PEDV to their offspring.

MO685PRESENCE OF SARS-COV-2 ANTIBODIES IN SPENT PERITONEAL DIALYSATE

Background and AimsInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits cellular and humoral immune responses. In patients with coronavirus disease 2019 (COVID-19), IgM, IgA, and IgG antibodies against SARS-CoV-2 emerge within a few days and can be detected in several body fluids, such as serum and oral fluids. End Stage Kidney Disease patients are especially vulnerable in this pandemic as they are immunocompromised, putting them at higher risks of infection and impaired response to vaccines. While repeated blood draws in hemodialysis patients pose no substantial medical or logistic problems, the situation is different in those treated by peritoneal dialysis. To overcome that limitation, we explored the presence or absence of SARS-CoV-2 antibodies in spent peritoneal dialysate in patients treated with acute and chronic peritoneal dialysis, respectively.MethodWe analyzed spent PD dialysate samples from four distinct patient groups, namely Pre-Covid-19 controls (Group 1; 15 samples collected between May 2019 and Feb 2020), Covid-19 negative controls during ongoing pandemic (Group 2; 33 samples collected between March and September 2020); chronic PD patients with confirmed Covid-19 (Group 3; 30 samples collected between March and September 2020,); and patients with confirmed Covid-19 and acute kidney injury treated with acute PD (Group 4; 18 samples collected in April 2020).SARS-CoV-2 IgG titer in spent PD dialysate was measured by enzyme-linked immunosorbent assay (ELISA) targeting Nucleocapsid (N) protein of SARS-CoV-2 virus (MPBIO cat#: 08440100). Total SARS-CoV-2 antibodies (IgG, IgM, and IgA) were measured using ELISA targeting recombinant N Protein and Spike protein (S Protein) (AFFYPRO Cat#: EA821). Absolute IgG concentration was calculated using IgG standard provided by the MPBIO ELISA kit. The total antibody titer was calculated as a relative value to the mean of antibody levels of COVID-19 negative patients. To account for different dialysate and ultrafiltration volumes, antibody titers were also normalized to total protein concentrations in the spent dialysate samples. The ratio of IgG or total antibody to total protein reflects the normalized titer.ResultsNormalized anti-SARS-CoV-2 IgG titer in the four groups is illustrated in Figure 1A. The mean IgG/protein levels in Group 3 and Group 4 are 86-fold (p=0.023) and 220-fold (p=0.0003), respectively, above the mean IgG/protein levels in COVID negative patients (Group 1 and 2 combined). The discrimination between patients with and without COVID-19 is excellent (AUC 0.938). At a threshold of 0.0024%, the sensitivity and specificity are 89.6% and 97.9%, respectively (Figure 1B). Using same threshold as Figure 1B, in Group 3, 9 out of 11 patients had a positive IgG response in all samples. In 5 patients, IgG levels decreased over time. The mean normalized total antibody/protein levels in Group 3 and Group 4 are 7.3-fold and 24-fold above those in COVID negative patients (combined Group 1 and 2; both p<0.001). Distribution pattern, ROC analysis, and dynamic change over time of total SARS-CoV-2 antibodies are like those of IgG (Figure 1D-F).ConclusionCovid-19 serology tests can provide much information including diagnosis, immune response, local seroprevalence, et al. Currently, most of serology tests are done using blood-related specimens. To our knowledge, this is the first study reporting SARS-CoV-2 antibodies in spent PD dialysate. Presence of SARS-CoV-2 antibodies in spent PD dialysate of peritoneal dialysis patients potentially provides a new way to perform frequent serology tests for this high-risk group. As USA is moving fast on national vaccination at this moment, using test strip developed for PD effluent to quickly and frequently check SARS-CoV-2 antibody in PD effluent could be used to monitor the vaccination efficiency while avoiding clinic visit.

MO875SEROCONVERSION RATE AND PERSISTANCE OF IGG RESPONSE TO SARS-COV2 IN HEMODIALYSIS PATIENTS. A CASE SERIES STUDY

Background and AimsHigher incidence and worse outcome of coronavirus disease (COVID-19) are observed in dialysis patients, mainly due to weak immune response. However, little is known about seroconversion ability and duration of antibody response after COVID-19 in this group. The aim of this study was to estimate the seroconversion rate and the persistence of IgG response to SARS-CoV2 in dialysis patients.MethodFour (4) dialysis patients previously infected with SARS-CoV2 were included in this study. Initially, all patients were tested for the presence of IgG antibodies 21-35 days after the onset of their symptoms. The cut-off value for positivity was a ratio of ≥ 1.4. Those patients with at least two consecutive positive samples were defined as seropositives. Seropositives were then having their antibodies tested monthly for a maximum period of six months or until the first negative result. Duration of antibody persistence was defined as the time between the day IgG were last detected and the day of onset of infection.ResultsAll four patients were seropositives after the initial test (seroconversion rate = 100%) with a mean IgG ratio of 6.44 (±1.28). Median follow up period was 128 (range 96-193) days. Median duration of antibody persistence was 153 (range 103-193) days. By the sixth month, IgG had turned negative in two of four patients (rate = 50%).ConclusionIn our study, dialysis patients showed a remarkable seroconversion rate after infection with SARS-CoV2. However, a rapid decline of IgG antibodies was observed in half of them.

AB0125 CLINICAL CHARACTERISTICS OF RHEUMATOID ARTHRITIS PATIENTS WITH IGG4-RELATED SYNOVITIS

Background:Elevated serum IgG4 (sIgG4) and IgG4+ plasma cell tissue infiltration are outstanding features of IgG4-related disease (IgG4-RD). However, elevated IgG4 is not specific for IgG4-RD. Our previous study reported elevated sIgG4 in 46% of rheumatoid arthritis (RA) patients (Mediators Inflamm 2014). Whether synovium from RA patients show similar characteristics of IgG4-RD and how about the clinical characteristics of RA patients with IgG4-related synovitis have not been reported yet.Objectives:To explore the serum and synovial IgG4 level and their correlation with disease indicators in RA.Methods:Active RA patients who underwent needle synovial biopsy with qualified synovium tissue were recruited. Demographic and clinical data were collected simultaneously. Synovium tissue were stained with H&amp;E for Krenn synovitis score and immunohistochemistry for positive cell densities of CD20, CD38, IgG and IgG4. Serum IgG4 level was detected by immunonephelometry.Results:Among 96 RA patients recruited, 74 (77.1%) were female, the median age was 55.0 (46.0~61.0) years, disease duration was 42.0 (12.0~120.0) months and SDAI was 31.2 (22.1~42.8).The median sIgG4 was 1.38 (0.86~2.42) g/L and 49(51.0%) patients had elevated sIgG4. Compared with those with normal sIgG4, RA patients with elevated sIgG4 had significantly higher levels of PrGA [7 (5~8) vs. 6 (4~7)], ESR [90 (64~116) mm/h vs. 61 (38~75) mm/h], CRP [46.20 (17.20~74.20) mg/L vs. 18.90 (9.46~49.20) mg/L], DAS28-ESR [6.3 (5.6~7.4) vs. 5.7 (4.7~6.4)], SDAI [34.2 (25.3~48.8) vs. 27.8 (18.9~35.9)] and HAQ-DI [1.70 (0.61~2.28) vs. 0.88 (0.40~1.75), all P&lt;0.05]. Meanwhile, they also showed significantly higher synovial counts of CD38+ plasma cells [1240(559~2290) /mm2 vs. 1020(354~1777) /mm2], IgG4+ plasma cells [106 (39~249) /mm2 vs. 68 (3~123) /mm2], and higher ratio of IgG4+/IgG+ plasma cells [26.3 (15.5~38.0) % vs. 15.2 (0.9~24.7) %, all P&lt;0.05].The median IgG4+ plasma cells count was 83 (10~192) /mm2 and median ratio of IgG4+/IgG+ plasma cells was 19.1 (8.4~31.5)%. Both of them correlated positively with ESR, CRP and sIgG4 (r=0.216~0.394, all P&lt;0.05). There were 46 (47.9%) patients with IgG4+ plasma cells &gt;10/HPF, who had significant higher ESR [86 (50~109) mm/h vs. 65 (40~84) mm/h] and CRP [43.35 (16.93~77.85) mg/L vs. 26.15 (9.54~52.53) mg/L, both P&lt;0.05] than those with IgG4+ plasma cells ≤10/HPF. There were 13 (13.5%) patients with the ratio of IgG4+/IgG+ plasma cells &gt;40%, and 11 (11.5%) patients with both IgG4+ plasma cells &gt;10/HPF and IgG4+/IgG+ plasma cells ratio &gt;40% (IgG4-related synovitis). RA patients with IgG4-related synovitis had significant higher ESR than the others [106 (53~125) mm/h vs. 69 (41~91) mm/h, P&lt;0.05].There were 10 (10.4%) patients showing elevated sIgG4 and IgG4-related synovitis. Four patients completed 1-year follow-up and all of them achieved remission at 6th month (SDAI≤3.3, Figure 1). Only one patient had radiographic progression at 12th month.Figure 1.Dynamic disease activity of 4 RA patients with elevated sIgG4 and IgG4-related synovitis during 1-year follow-up.Conclusion:IgG4-related synovitis can be found in RA patients. Their clinical significance in disease characteristics and outcomes are worth further study.Acknowledgements:This work was supported by National Natural Science Foundation of China (no. 81971527, 81801606 and 81801605), Guangdong Natural Science Foundation (no. 2018A030313541 and 2018A030313690), Guangdong Medical Scientific Research Foundation (no. A2018062), Guangdong Basic and Applied Basic Research Foundation (no. 2019A1515011928 and 2020A1515110061), and Science and Technology Program of Guangzhou (no. 201904010088).Disclosure of Interests:None declared

AB0853 IGG4-RELATED DISEASE CAUSING OCULAR NERVE PALSIES AND ORBITAL APEX SYNDROME: CASE REPORT AND LITERATURE REVIEW

Background:IgG4-Related Disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory condition. The epidemiology is not well defined: it usually affects adults from middle-age onwards, predominantly male. Both B and T-cells are central in IgG4-RD pathogenesis, as demonstrated by the efficacy of B-cell depletion therapy.IgG4-RD can affect multiple organs including the central and peripheral nervous system, producing a constellation of clinical symptoms and signs, depending on the organ structures involved.IgG4-related orbital disease is relatively rare can implicate all extra-ocular muscles, structures emerging from the Orbital apex, optic canal, or superior and inferior orbital fissure. Depending on the structures involved, it can produce different or sometimes subtle clinical presentations, posing diagnostic challenge. There were case reports of IgG4-related ophthalmic disease misdiagnosed as intraocular tumour.Objectives:IgG4-RD is increasingly recognised as an entity affecting the head and neck region. However, it rarely involves skull base and presents with orbital apex syndrome. In this current case report, we describe an interesting case of IgG-related orbital disease presenting with ocular nerve palsies and orbital apex syndrome.Methods:Case report.Results:A 36-year-old gentleman with cocaine and alcohol misuse presented with a 2-month history of left sided headache, diplopia, recurrent ear infections, otalgia and hearing loss. Initial imaging suggested left otomastoiditis and intravenous antibiotics were commenced. Contralateral partial third nerve palsy with pupil sparing was elicited. 2 months later, there was worsening right eye ptosis, proptosis, right relative afferent pupillary defect, reduced visual acuity and colour vision as well as a near-complete ophthalmoplegia. Subsequent imaging showed worsening soft tissue swelling centred on the upper left parapharyngeal and masticator space, with multiple perineural enhancement and lateral extension to right orbital apex and orbital fissures. Blood tests only revealed raised IgG4 subclass. Infectious aetiology was excluded. Left nasal mass biopsy performed showed no fungal organism or malignancy. There were lymphoplasmacytic proliferation but no storiform fibrosis or obliterative phlebitis. IgG4 immunostaining on two assessable fields revealed 22 and 17 positive plasma cells respectively, and an IgG4: IgG ratio of &lt;10%, and 50% in the other. Significant improvement was seen clinically and radiologically with antibiotics and a tapering regime of oral Prednisolone. Patient was commenced on Azathioprine as long term immunosuppression.Conclusion:A high degree of clinical suspicion is necessary to diagnose IgG4-RD when presenting with orbital apex syndrome and ocular nerve palsies,IgG4-RD can mimic mastoiditis of infectious aetiology. Other differentials may include cocaine-induced midline destructive lesions and granulomatosis with polyangiitis. The diagnosis can be supported by elevated serum IgG, elevated IgG index and pathognomonic histopathological findings. . The diagnosis of IgG4-related orbital disease should be deliberated on by a multidisciplinary group, with every effort being made to exclude an infectious aetiology, before embarking on immunosuppressive therapy.Primary treatment is with steroids. However, immunotherapy using azathioprine can be utilised in recurrent disease or patients with steroid intolerance.

The evaluation of the relationship between antibody response and COVID-19 disease severity

Background: World Health Organization (WHO) reported COVID-19 as a pandemic, on March 11th, 2020. The quick and accurate diagnosis is crucial to provide the appropriate treatment and isolation process. Immunity against COVID-19 is essential for disease control. There is scant information about antibody response and disease severity. In this study, we aimed to investigate the relationship between clinical severity and COVID antibody response. &#x0D; Methods: Hospitalized PCR (n=10) and/or radiologically (n=31) proven 35 COVID-19 patients were included in the study. The blood samples were collected at least eight days after the onset of symptoms and studied by using the COVID-19 IgG/IgM Rapid Test. Patients were divided as mild (n= 14), severe (n=12) and critical (n=9) according to COVID-19 disease severity. The results were compared among the groups. &#x0D; Results: A total of 35 COVID-19 patients’ (mean age: 54.65±16.51 years, Male/Female: 23/12) rapid test results were compared according to clinical severity. A significant correlation was observed between disease severity and IgG results in both PCR positive (p=0.007) and whole patients (p=0.026). The positive IgG ratio was significantly low in the mild patient group while it was higher in severe and critical patients. &#x0D; Conclusions: Our study reveals that the greater antibody response occurs with the more serious COVID-19 disease. The application of the rapid test, in addition to PCR, may be used as a clue to foresee the clinical progression. These tests not only have an important role in diagnosis with PCR tests but also are associated with disease severity.

Immunization With a DNA Vaccine Encoding the Toxoplasma gondii' s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model.

Toxoplasma gondii, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of T. gondii GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic T. gondii infection was assessed by observing the survival time after challenge with the highly virulent T. gondii RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of T. gondii (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-γ, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4– T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-β1, IL-1β, and the transcription factor factors RORγt, RORα, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (p > 0.05). These effective immune responses had mounted protective immunity against T. gondii infection, with a prolonged survival time (16.80 ± 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic T. gondii infection.