IgG4 Measurement Research Articles

Sociodemographics, Clinical Factors, and Biological Factors Associated with Loiasis in Endemic Onchocerciasis Areas in Southern Gabon.

To implement the appropriate strategies for scale-up interventions to eliminate onchocerciasis without severe adverse events, clinical and biological factors associated with loiasis were analyzed in onchocerciasis-endemic areas. Blood was collected from volunteers after examination by a physician. Detection of microfilariae and measurement of Ov16 IgG4 were performed using direct microscopic examination of blood and onchocerciasis rapid test detection, respectively. Areas with sporadic, hypoendemic, and hyperendemic onchocerciasis endemicity were found. Participants with microfilaremia were considered microfilaremic, and those without microfilaremia were seen as amicrofilaremic. Of the 471 study participants, 40.5% (n = 191) had microfilariae. Among them, Mansonella spp. was the most common (78.2%, n = 147), followed by Loa loa (41.4%, n = 79). The association between the two species represented 18.3% (n = 35). The specific immunoglobulins of Onchocerca volvulus were detected in 24.2% of participants (n = 87/359). Overall prevalence of L. loa was 16.8%. Hypermicrofilaremia was found in 3% (N = 14), and one participant had more than 30,000 microfilaremiae per milliliter. The frequency of L. loa did not vary according to the level of onchocerciasis transmission. Pruritus was the most common clinical sign (60.5%, n = 285) reported, mainly in microfilaremic participants (72.2%, n = 138/191). The prevalence of L. loa microfilaria in the study population was below the threshold at risk for the occurrence of serious side effects due to ivermectin. Clinical manifestations frequently observed could be exacerbated by microfilaremia in areas where onchocerciasis transmission is high.

Main Diagnostic Criteria Usually Does Not Work for Autoimmune Pancreatitis Wrongly Presuming Malignancy.

Autoimmune pancreatitis (AIP) usually responds dramatically to steroid therapy. Occasionally, however, misdiagnosed patients have undergone pancreaticoduodenectomy. This study is aimed at providing useful information to improve the accuracy of diagnosis before surgery and thus avoid unnecessary resections in patients with AIP. From January 2015 to February 2020, a series of patients were enrolled, having undergone pancreaticoduodenectomy for presumed malignancy. AIP diagnoses were confirmed by postoperative pathology. The demographic and clinical data of the AIP patients were evaluated. The main diagnostic criteria (HISORt, Asian, and ICDC) for AIP were applied to assess whether and how unnecessary surgery could have been avoided. A total of 124 cases of pancreaticoduodenectomy were performed for presumed malignancy. Six patients were diagnosed with benign disease and five with AIP. The prevalences of benign disease and AIP were 4.8% and 4%, respectively. Four patients were female and 1 male, with a mean age of 60.0 years old. Jaundice, pain, and weight loss were observed in 100%, 20%, and 40% of AIP patients, respectively. The radiologic features of the AIP patients were a diffusely enlarged gland (40.0%), a focally enlarged gland (40.0%), pancreatic ductal dilatation (60.0%), upstream parenchymal atrophy (20.0%), bile duct thickening (66.0%), and bile duct stricture (40.0%). Based on the diagnostic criteria for AIP, surgery could have been avoided in two cases. IgG4 measurement and integrated use of major diagnostic criteria should be emphasized in every patient eligible for pancreaticoduodenectomies.

Pre-seasonal immunotherapy is effective in both monosensitized and polysensitized patients with allergic rhinitis.

Background. The effectiveness of pre-seasonal allergoid immunotherapy in polysensitized patients are not well-known. The aim of the present study was to compare the clinical efficacy and immunological changes of pre-seasonal allergoid immunotherapy in mono and polysensitized patients with grass pollen allergy. Methods. Fourty six patients with seasonal allergic rhinitis undergoing pre-seasonal grass pollen immunotherapy and 28 cases followed by conventional drug treatment were included. These groups were divided into monosensitized and polysensitized ones. All patients were followed between March-September with symptom-medication scores, and visual analogue scale (VAS). The quality of life was assessed using the Mini-RQLQ questionnaire. Phleum pratense (Phl p) specific IgE and IgG4 (UNI-CAP 100, Phadia) measurements were performed before and after 7 weeks of immunotherapy. Results. In the immunotherapy group, 15th weekly symptom-medication scores and VAS scores between May and August were found to be significantly lower than those in the control group (p < 0.05). Phl p specific IgE and IgG4 levels were significantly higher after immunotherapy compared to those before immunotherapy (p = 0.001). Furthermore, Phl p specific IgG4 levels after immunotherapy were also significantly higher than in the control group (p = 0.001). Improvements in activities-practical problems and non-nose/eye symptoms quality of life scores were significantly different between two groups (p < 0.05). There was no difference in terms of clinical and immunological parameters in mono- and polysensitized patients (p > 0.05). Conclusions. This study indicates that clinical improvement with pre-seasonal grass pollen immunotherapy is accompanied by important increase in specific IgG4 blocking antibodies. Furthermore, a single-allergen immunotherapy can lead to similar clinical efficacy and immunological changes in polysensitized as well as monosensitized patients with grass pollen allergy.

IgG4 antibodies against Bm14 as an evaluation tool of mass drug administration in a co-endemic area of Brugia timori and Wuchereria bancrofti

To evaluate the success of mass drug administration for lymphatic filariasis, WHO has recommended two rapid tests, Brugia Rapid (BR) to detect the presence of IgG4 antibodies against Brugia sp and Filariasis Test Strip (FTS) to detect antigens of Wuchereria bancrofti. As a country co-endemic for Brugia sp. and W. bancrofti, Indonesia needs a single diagnostic tool that can detect the exposure to both species. This study aimed to evaluate the efficacy of mass drug administration by measuring Bm14-specific IgG4 levels in blood samples of the population living in a co-endemic area of B. timori and W. bancrofti in Southwest Sumba Regency. A total of 132 plasma samples obtained before and one year after DEC-albendazole administration, which have been previously tested with BR and FTS, were examined for IgG4 against Bm14 using enzyme-linked immunosorbent assay. The results showed that before treatment all 32 individuals (100%) with BR+/ FTS+ were also positive for Bm14-specific IgG4, while in BR+ or FTS+ group there were >90% samples detected positive. At one year after treatment, positive results for Bm14-specific IgG4 were still detected in 96.9% samples with BR+/ FTS+, 78.8% samples with BR+/ FTS- and 82.9% samples with BR-/ FTS+. On the other hand, the BR-/ FTS- group also had high rate of Bm14-specific IgG4 positivity either before treatment (62,5%) and at one year after treatment (43.8%). The lowest decrease of Bm14-specific IgG4 positivity at one year after treatment was shown in the double positive group (3.1%), while the highest was in the double negative group (18.7%). The measurement of IgG4 against Bm14 has the potential as a sensitive diagnostic tool to evaluate the success of MDA in the areas co-endemic for B. timori and W. bancrofti.

Array-based measurements of aero-allergen-specific IgE correlate with skin-prick test reactivity in asthma regardless of specific IgG4 or total IgE measurements

Skin prick testing (SPT) and measurement of serum allergen-specific IgE (sIgE) are used to investigate asthma and other allergic conditions. Measurement of serum total IgE (tIgE) and allergen-specific IgG4 (sIgG4) may also be useful. The aim was to ascertain the correlation between these serological parameters and SPT. Sera from 60 suspected asthmatic patients and 18 healthy controls were assayed for sIgE and sIgG4 reactivity against a panel of 70 SPT allergen preparations, and for tIgE. The patients were also assessed by skin prick tests for reactivity to cat, dog, house dust mite and grass allergens. Over 50% of the patients had tIgE levels above the 75th percentile of the controls. 58% of patients and 39% of controls showed sIgE reactivity to ≥1 allergen. The mean number of allergens detected by sIgE was 3.1 in suspected asthma patients and 0.9 in controls. 58% of patients and 50% of controls showed sIgG4 reactivity to ≥1 allergen. The mean number of allergens detected by sIgG4 was 2.5 in patients and 1.7 in controls. For the patients, a strong correlation was observed between clinical SPT reactivity and serum sIgE levels to cat, dog, house dust mite (HDM) and grass allergens. SPT correlations using sIgE/sIgG4 or sIgE/tIgE ratios were not markedly higher. The measurement of serum sIgE by microarray using SPT allergen preparations showed good correlation with clinical SPT reactivity to cat, dog, HDM and grass allergens. This concordance was not improved by measuring tIgE or sIgG4.

Is Peyronie's an IgG4-related disease?

We believe that IgG4 may have a role in the pathogenesis of Peyronie's disease (PD), and this role could be particularly beneficial for developing new strategies; therefore, we aimed to investigate the role of IgG4 in PD. This study included 3 groups with a total of 139 subjects: (I) PD group (n=61), (II) control group (n=48), and (III) benign prostatic hyperplasia (BPH) group (n=30). IgG4 measurement was performed using the enzyme-linked immunosorbent assay. Plaque size, penile curvature, and the presence of concomitant impotence were evaluated in the PD group. Impotence was assessed based on the International Index of Erectile Function (IIEF). A significant difference was observed between the PD and control groups and between the PD and BPH groups with regard to IgG4 levels, while no significant difference was found between the BPH and control groups (p=0.0001, p=0.002, and p=0.07, respectively). The IgG4 levels were significantly higher in the PD than in the other groups. The cutoff value determined between the groups was 87.5, 82, and 31.5, respectively. Mean plaque size was 2.0±1.01 cm, and a significant relationship was found between plaque size and IgG4 concentration (p=0.02). Mean penile curvature was 35.6±25.1°, and a significant relationship was found between penile curvature of >60° and IgG4 concentration (p=0.001). Mean IIEF score was 19 (range, 7-25). Moreover, no significant relationship was found between erectile dysfunction and IgG4 concentration. Penile pain was present in 24 (39.3%) patients with PD. The IgG4 levels were significantly increased in patients with PD, which implies that IgG4 may have a role in the pathogenesis of PD. This finding could be particularly beneficial for developing new strategies. Future studies with larger patient series are needed to substantiate our findings.

Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass.

The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

A Rare and Atypical Complication of Chronic Pancreatitis

Question: A 63-year-old woman with a past medical history of idiopathic chronic pancreatitis and orthotopic heart transplant requiring chronic immunosuppression presented to the emergency department with 3 days of nausea, vomiting, diarrhea, and an inability to tolerate oral intake. The patient had epigastric pain radiating around her abdomen to her back that was exacerbated by eating. A workup for the etiology of the patient’s chronic pancreatitis, including a review of her history (negative for heavy alcohol consumption) and medications as well as measurement of triglyceride levels and IgG4, had revealed no underlying cause.

Limited diagnostic value of total serum IgG4 measurements in adult patients

Limited diagnostic value of total serum IgG4 measurements in adult patients

Variable and inaccurate serum IgG4 levels resulting from lack of standardization in IgG subclass assay calibration.

Background The quantification of serum IgG4 is commonly performed during the diagnostic workup of IgG4-related diseases (IgG4-RD). According to recent literature, IgG4 values above 1.35 g/L are characteristic of IgG4-RD and support its diagnosis at initial presentation. The purpose of this study was to evaluate comparability and accuracy of the two main commercially available IgG4 assays (Siemens Healthineers and The Binding Site). Methods Method comparison was performed for IgG and IgG subclasses using a collective of selected samples with elevated serum IgG4. In addition, we assessed the accuracy of both assays using purified polyclonal and monoclonal IgG4 preparations. Results Our data show significant discrepancies between the two IgG subclass assays for the measurement of IgG4 and, to a lesser extent, IgG3. Conclusions The lack of standardization between the two main providers of commercially available IgG4 assays leads to significant inter-assay result discrepancies, which might potentially cause unnecessary clinical workup. We conclude that serum IgG4 assay-specific decision limits, and not an assay-independent single cut-off level for IgG4 (e.g. 1.35 g/L), should be used when assessing patients for IgG4-RD. An internationally recognized, certified reference material for IgG subclasses is urgently needed, and assay manufactures are encouraged to undertake steps toward standardization of measurements of IgG4 and other IgG subclasses.

The diagnostic value of serum IgG4 for the diagnosis of IgG4-related disease: and is that so great?

IgG4-related disease (IgG4-RD) is a systemic immune mediated condition that is characterized by the formation of tumor-like fibroinflamma-tory foci in different organs and by the elevation of serum and tissue IgG4 levels in the majority of patients. The pathogenesis of the disease, including the role of IgG4, has not been established exactly. Serum and tissue IgG4 hypersecretion is a nonspecific sign and occurs in many rheumatic, infectious, and malignant diseases. Objective : to determine the range of nosological entities associated with the increase in serum IgG4 levels, as well as the frequency and nature of this increase in patients with IgG4-RD. Patients and methods . The results of all serum IgG4 measurements carried out in the Laboratory of Immunology and Molecular Biology of Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, in 2017—2018 were analyzed. Serum IgG4 parameters were separately estimated in 52 patients with verified IgG4-RD according to the universal diagnostic criteria proposed by H. Umehara et al (2011). Results and discussion . In 2017—2018, a total of247patients were tested for serum IgG4 levels. The latter were elevated in 76 (30.8%) patients, but only 28 (36.8%) were diagnosed as having IgG4-RD. Along with IgG4-RD, antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) were characterized by increased serum IgG4 levels. The highest median IgG4 level was found in patients with a verified diagnosis of IgG4-RD: 6.31 vs 3.2, 3.22, and 2.69 g/L in ANCA-associated vasculitis, RA, and SLE, respectively. In 52 patients with IgG4-RD, the IgG4 level >1.35 g/L was found in 88% of cases. The median serum IgG4 level was 3.45 g/L (2.1; 11.4). The highest level was observed in patients with generalized lymphadenopathy and in those with IgG4-related sialoadenitis and dacryoadenitis (Mikulicz disease). The serum IgG4 level was positively correlated with the number of affected organs (Spearman's correlation coefficient, 0.39; p=0.0056, Student's t-test). All the patients showed a tendency towards decreasing serum IgG4 levels during treatment regardless of its clinical response; however, the levels returned to normal only in 73% after 12 months of treatment. Conclusion . The increased serum and tissue IgG4 concentration is not specific, but at the moment it is the only disease marker available in clinical practice. To correctly interpret the diagnosis, it is necessary to assess the entire set of clinical manifestations, imaging data, and morpholopathological findings.

IgG4 subclass and gamma-glutamyl transferase in children with ulcerative colitis with primary sclerosing cholangitis and without sclerosing cholangitis.

Aim of the studyPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which could be associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The aim of this study was to compare GGT and IgG4 levels among children with UC with PSC and without PSC.Material and methodsIn this cross sectional study children with UC with PSC and UC without PSC were included. Serum immunoglobulin G4 (IgG4) and gamma-glutamyl transpeptidase (GGT) levels of the 90 UC patients with and without concomitant PSC were measured. Children with serum IgG4 concentration > 175 mg/dl were considered to have elevated IgG4.ResultsElevated serum IgG4 was found in 8 of 30 (26.6%) patients with PSC vs. 3 of 60 (5.0%) patients without PSC. Compared with the group without symptoms of PSC, the group with PSC showed significantly higher levels of aspartate aminotransferases (AST; 22.5 U/l vs. 70.0 U/l, p < 0.001), alkaline phosphatase (ALP; 359.0 U/l vs. 602.0 U/l, p < 0.001), and IgG4 (56.0 vs. 73.0, p = 0.02). The odd ratio of the elevated IgG4 and GGT in predicting PSC was 6.9 (95% CI: 1.6-28.4) and 18 (95% CI: 5.7-55.9), respectively.ConclusionsAST, alanine aminotransferase (ALT), GGT, ALP, and serum IgG4 were significantly higher in UC patients with sclerosing cholangitis (SC) compared to UC patients without SC. GGT and IgG-4 measurements are recommended for evaluation of UC.

A surveillance system for lymphatic filariasis after its elimination in Sri Lanka

Lymphatic filariasis (LF) has been declared eliminated in Sri Lanka in September 2016. To maintain elimination status, a surveillance system to detect hidden endemic foci or LF resurgence is of highest priority. In this paper, we have reported an investigation of LF transmission in Trincomalee district where a surveillance program was not carried out due to 30 years of civil unrest. Proposed surveillance system included, measurement of anti-filarial IgG4 in urine of schoolchildren in areas where LF transmission could exist and assessment of circulating filarial antigen (CFA) and microfilaria (mf) in all urine antibody positive schoolchildren, their family members and 10–15 neighbours of each urine antibody positive household. Spatial distribution of the anti-filarial antibody titers in urine in a high antibody suspected area was analyzed using GPS logger data. Among 2301 school children from 11 schools studied, 41 (1.8%) urine antibody positives were found. The antibody positive rates of the schools ranged between 0 and 4.0%. Nine of the 630 (1.4%) examined became positive for CFA but were negative for mf. Although there were no mf positives, positive CFA and antibody results indicated the existence of Wuchereria bancrofti in Trincomalee. Highest antibody titres in an area correlated with the prevalences of urine antibodies and CFA. Spatial analysis showed LF transmission foci. Therefore, a combination of the non-invasive methods, urine ELISA and GPS mapping, will be a new effective surveillance system to identify hidden LF transmission foci.

Hashimoto's thyroiditis with elevated serum IgG4 concentrations is not equivalent to IgG4 Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non-IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT. Both thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF-β1 in thyroid tissues were detected by immunohistochemistry. Patients with HT were divided into two groups: elevated serum IgG4 HT (n=12) and nonelevated serum IgG4 HT (n=81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P=.023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF-β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P=.756). The measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT.

Utility of Serum IgG4 Levels in a Multiethnic Population

BackgroundIgG4-related disease (IgG4-RD) is a recently recognized condition defined by characteristic histopathologic findings in affected organs. Serum IgG4 concentration is often but not always elevated. The sensitivity and specificity of serum IgG4 vary greatly across studies and has been anecdotally associated to ethnicity. Our study was conducted to investigate the difference in serum IgG4 levels between Asian and non-Asian patients with IgG4-RD. MethodsThis is a single-center retrospective study of 26 Asian and 10 non-Asian patients with histologically confirmed IgG4-RD. Serum IgG4 levels, clinical features and other laboratory findings were compared between the 2 groups, 31 Asian and 11 non-Asian patients with non-IgG4-RD rheumatic diseases were randomly identified to evaluate test characteristics of serum IgG4 measurement. ResultsMedian serum IgG4 at time of diagnosis was significantly higher in Asian (median = 11.2g/L, interquartile range: 4.6-19.7) than non-Asian patients (median = 2.9g/L, interquartile range: 0.7-5.4, P = 0.0094), as well as the median serum IgG and total protein. Asian patients had more eosinophilia and polyclonal hypergammaglobulinemia than non-Asian patients (P = 0.016 and 0.001, respectively). Test sensitivity was higher in Asian (96%) than non-Asian patients (67%), whereas test specificity was higher in non-Asian patients (91% versus 71%). ConclusionAsian patients with IgG4-RD have more exuberant serum IgG4, IgG and polyclonal hypergammaglobulinemia than non-Asian patients; the mechanism of this difference requires further study. These findings have significant clinical importance and must be accounted for in the diagnostic workup of patients in multiethnic settings.

A study of serum IgG4 levels in the clinical metamorphosis of autoimmune thyroid disease

BackgroundMeasurement of serum IgG4 had been suggested to distinguish the unique subtypes of autoimmune thyroid disease (AITD) which demonstrated patterns of fluctuating between hyperthyroidism and hypothyroidism. However, the clinical utility of serum IgG4 measurement is inconclusive due to few studies having addressed these unusual patients compared with the specificity of serum IgG4 in healthy patients. AimTo investigate whether elevated serum IgG4 levels could be used as a marker to identify fluctuating AITD patients. Materials and Methods20 AITD patients who evolved from hyperthyroid Graves’ disease to spontaneous hypothyroidism or vice versa were compared with 40 healthy subjects, 40 patients with hyperthyroid Graves’ disease (GD) and 40 patients with subclinical or overt hypothyroid Hashimoto’s thyroiditis (HT). Serum levels of total IgG and IgG4 were measured and the proportion of elevated serum IgG4 levels (defined by serum IgG4 levels≥135mg/dL) was compared with control patients. ResultsA series of 20 Thai patients with clinical evolution of AITD was analyzed with a median follow-up at 92months (range 3–380months). Elevated serum IgG4 levels were not found in fluctuating AITD patients but were found in 5% of the control GD patients, 2.5% of the control HT, and 2.5% of healthy subjects which were not statistically significant between each group. ConclusionOur results contrasted with those of previous studies from Japan which reported elevated serum IgG4 as a marker to identify subset of AITD patients. At present, the clinical utility of serum IgG4 measurements in AITD is inconclusive and requires further investigation.

Clinical features and predictive value of serum inflammatory markers of perivascular involvement in immunoglobulin G4-related disease.

Vascular and/or perivascular involvements of sclerotic inflammation (perivasculitis) are a complication of immunoglobulin G4-related disease (IgG4-RD). We sought to examine clinical manifestations of perivasculitis by computed tomography (CT) in patients with elevated serum IgG4 levels, and then to evaluate some potential predictors of perivasculitis in definite IgG4-RD patients. From a database of patients with serum IgG4 measurements, we selected 81 patients with elevated serum IgG4 levels (≥135mg/dl). Perivasculitis was defined radiologically as thickened contrast-enhanced rind surrounding the aorta and its major artery on CT imaging. We found 15 patients with perivasculitis; 10 patients in the definite (n=37), four in the possible (n=18), and one in the excluded (n=26) IgG4-RD groups. Clinical predictors of perivasculitis were investigated in 34 untreated patients with definite IgG4-RD. Patients with perivasculitis (n=10) had significantly higher age at diagnosis (74.2±8.8 vs 63.5±9.9years, P=0.006), higher levels of serum IgG4 (754 vs 292mg/dl, P=0.007) and C-reactive protein (CRP, 0.52mg/dl vs 0.10mg/dl, P=0.001) than patients without perivasculitis (n=24). The sensitivity and specificity of serum CRP ≥0.25mg/dl for identifying perivasculitis in the definite IgG4-RD group were 100 and 71%, respectively (area under the receiver operating characteristic curve 0.863). Our results indicate that IgG4-related perivasculitis was associated with elevated levels of serum CRP and older age, and that CRP may be a useful marker for detecting perivascular involvement in IgG4-RD.

IgG4-Related Lung Disease: Retrospective Review of 9 Cases

SESSION TITLE: Pulmonary Manifestation of Systemic Disease SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: IgG4-related disease is a corticosteroid-responsive systemic fibroinflammatory disease that affects various organs. Although pancreatic involvement is the most common presentation, pulmonary manifestation, known as IgG4-related lung disease (IgG4-RLD) has been increasingly recognized. While many reports are from Asian populations, we aimed to clarify the clinical and pathologic aspects of IgG4-RLD in non-Asian populations. METHODS: A retrospective review was conducted of cases with biopsy-proven IgG4-RLD encountered from January 1994 till February 2016 at an academic medical center. IgG4-RLD was defined as meeting at least 2 out of 3 characteristic histopathological features (IgG4-positive lymphoplasmacytic infiltration, fibrosis, and obliterative phlebitis) with IgG4+ cell counts of more than 50 per high power field (HPF) in either surgical or nonsurgical specimens and IgG4+: IgG+ ratio of greater than 0.4 in combination with compatible clinicoradiologic features. We also included cases manifesting at least one histopathologic feature, IgG4+ cell counts per HPF of more than 50 in a surgical specimen or more than 20 in a nonsurgical specimen, with IgG4+: IgG ratio of greater than 0.4, if either elevated serum IgG4 level or initial favorable corticosteroid responsiveness (or complete surgical resection) was seen along with compatible clinicoradiologic features. RESULTS: A total of 9 patients with IgG4-RLD were identified, of which 8 were male and all were Caucasians. The median age at diagnosis was 64 years (interquartile range [IQR], 59-70). Serum IgG4 measurement was available in 8 patients, and the median peak serum IgG4 level was 234 mg/dL (IQR, 93-479). Five patients had respiratory symptoms on presentation, of which cough (N=4) and dyspnea (N=4) were most common, followed by nasal congestion (N=3). The main radiographic abnormality that led to biopsy was seen in the parenchyma (mass or nodule) in 7 patients, the central airway (stenosis) in 1 patient, and the pleura (pleural thickening and effusion) in 1 patient. The secondary radiographic abnormality was seen in 5 patients; 4 had mediastinal and/or hilar lymphadenopathy, and 1 had bronchial stenosis. The median count of IgG4+ cells was 65 (IQR, 49-117) per HPF, and the median IgG4+:IgG+ ratio was 0.56 (IQR, 0.47-0.74). No medical treatment was immediately necessary in 4 patients who underwent complete surgical resection of the pulmonary lesion. Among those patients; however, 3 had a recurrence of IgG4-RLD and received either corticosteroids or steroid-sparing agents during the clinical follow-up. The remaining 5 patients received corticosteroids immediately after the diagnosis of IgG4-RLD. All 5 patients subsequently developed either recurrence of IgG4-RLD or experienced the re-emergence of IgG4-related disease in the extra-pulmonary organs. CONCLUSIONS: IgG4-RLD is the pulmonary manifestation of IgG4-related disease, which commonly affects middle-aged or elderly men, with a high propensity for recurrence. Majority of patients present with mass or nodule with associated lymphadenopathy. CLINICAL IMPLICATIONS: IgG4-RLD mimics malignancy or other infectious or inflammatory conditions in its presentation. DISCLOSURE: The following authors have nothing to disclose: Reina Suzuki, Eunhee Yi, Jay Ryu, Hiroshi Sekiguchi No Product/Research Disclosure Information

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD.Conclusions: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

Falsely low immunoglobulin (Ig)G4 in routine analysis: how not to miss IgG4 disease.

Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning.