Manifestation Of IgG4-related Disease Research Articles

Identification of serum IFN-\u03b1 and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

Clinical case of membranous nephropathy in a patient with IgG4-related disease

IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.

IgG4-related disease in the abdomen and pelvis: atypical findings, pitfalls, and mimics.

IgG4-related disease (IgG4-RD) is a systemic, autoimmune, fibroinflammatory disease that can cause multi-organ damage. Although there have been many trials and studies since its recognition in 2003, there is still much that is unknown. Furthermore, IgG4-RD can affect any organ in the body and often has many mimics and alternative diagnoses, which can make for a challenging workup. Imaging plays a substantial role in the diagnosis of IgG4-RD and is often the first occasion where IgG4-RD comes into consideration. Thus, knowledge about the imaging findings of various manifestations of IgG4-RD can aid in the diagnosis and have a significant impact on patient management. In this article, we review the wide array of imaging findings, both typical and atypical, as well as possible mimics of IgG4-RD in the abdomen and pelvis.

The Frequency of SARS-CoV-2 Specific Memory B Cells in COVID-19 Recovered Patients Remain Stable While Antibodies Decay Over Time

The breadth of the humoral immune response following SARS-CoV-2 infection was indicated to be important for recovery from COVID-19. Recent studies have provided valuable insights regarding the dynamics of the antibody response in symptomatic COVID-19 patients. However, the information regarding the dynamics of the serological and cellular memory in COVID-19 recovered patients is scarce. It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection. Here, we describe the dynamics of both the SARS-CoV-2 specific serological and B cell response in COVID-19 recovered patients. We found that acute phase SARS-CoV-2 patients mount a rapid, robust antibody response following infection however, the serological memory decays in COVID-19 recovered patients over the period of six months. Using an in vitro neutralization assay revealed a strong correlation between total RBD-specific (RBD+) antibodies and neutralizing antibodies suggesting that antibody levels can be used as proxy to determine neutralizing capacity. In contrast to the antibody decay observed in recovered patients, the RBD+ memory B cell (mBC) frequency was found to be stable over time. Moreover, the frequency of RBD+ B cell plasmablasts (PB) was found to be associated with the RBD+ IgG levels. B cell receptor sequencing (BCR-Seq) of RBD+ PB show unregular high frequency of the IgG4 isotype which is known to contribute to the manifestation of IgG4 related disease and other autoimmune diseases. These data, suggests that the differentiation of short-lived PB to become long-lived plasma cells may be impaired and the main contributor of antibody production in recovered COVID-19 patient are the short-lived PB that predominantly encode to IgG4 subclass. The skewed class switch towards IgG4 may contribute to the severeness of the COVID-19 morbidity. Moreover, the persistence of RBD+ mBC following recovery may contribute to a robust recall humoral response in a case of re-infection by SARS-CoV-2. Overall, our data obtained in this study reveals a discordance between serological and cellular memory in COVID-19 recovered patients which has important implications on re-infection susceptibility and vaccine design.Ethical Approval: All patients provided informed consent to the use of their data and clinical samples for the purposes of the present study and blood collection was performed under institutional review board approvals number 0001281-4 and 0000406-1. All blood samples were collected at the Hasharon Hospital, Rabin Medical Center under ethical approval number 0265-20.

Diagnosis and treatment of IgG4-related pancreatitis

Immunoglobulin G (IgG)4-related pancreatitis, also named as type Ⅰ autoimmune pancreatitis, is recognized as a pancreatic manifestation of IgG4-related disease. It is very hard to differentiate it from pancreatic cancer due to similar clinical manifestations with pancreatic cancer. Diagnosis of IgG4-related pancreatitis mainly relies on pathological examination and imaging examination. Corticosteroids are the main treatment for IgG4-related pancreatitis, and the risk of relapse is still high with steroid taper or following withdrawal of steroids. Based on researches on IgG4-related pancreatitis and our clinical experience, the authors have analyzed and summarized pathogenesis, clinical manifestations, clinical diagnosis, differentiation from pancreatic cancer, clinical treatment of IgG4-related pancreatitis, and suggested that elucidation of its mechanism and induction of immunotherapy may improve its efficacy. Key words: IgG4-related pancreatitis; Diagnosis; Treatment

Inflammatory abdominal aortic aneurysms: place of Ig G4related diseases

Aim. Inflammatory abdominal aortic aneurysm may be one of the manifestations of Ig G4-related disease. This study analyzes the clinical manifestations of Ig G4related inflammatory abdominal aortic aneurysm. Material and methods. We examined twenty patients with abdominal aortic aneurysm (AAA). The clinical performance of the disease, the results of laboratory and pathomorphological studies were studied. In 8 cases, Ig G4-related inflammatory AAA criteria were identified. Results. Compared to atherosclerotic AAA, Ig G4-related cases were characterized by a less frequent presence of abdomen or back pain. The concentration of IgG4 in serum in Ig G4-related cases was significantly increased. Patients with Ig G4-related inflammatory AAA often had a history of allergic reactions to drugs, autoimmune diseases, a high concentration of Ig E and a high titer of antinuclear antibodies in blood serum. According to a histological study of intraoperative biopsy samples, Ig G4-related cases were characterized by thickening of adventitia and numerous infiltrates with Ig G4-positive plasma cells. Conclusion. The presence of Ig G4-related disease is diagnosed in the presence of irregular fibrous tissue proliferation with Ig G4 plasma cell infiltrates and with an increase in the concentration of Ig G4 in blood serum. Ig G4-related inflammatory AAA has clinical specifics in comparison with atherosclerotic aneurysm.

Rare Clinical Course of Immunoglobulin G4-Related Inflammatory Abdominal Aortic Aneurysm with Multiple Rare Complications

Immunoglobulin G4- (IgG4-) related inflammatory abdominal aortic aneurysm (AAA) has been recognized as a manifestation of IgG4-related disease (IgG4-RD). We experienced one patient with multiple consecutive manifestations before and after endovascular stent grafting for IgG4-related inflammatory AAA (IAAA). A 71-year-old man was diagnosed with IgG4-RD due to increased IgG4 serum concentration, typical findings of parotid gland biopsy, and periaortitis in another hospital 2 years and 7 months before visiting our hospital. He came to our hospital because of abdominal pain and IAAA. He developed paraplegia after hospitalization and underwent endovascular stent grafting for the IAAA. About one month after stent grafting, he developed perforation of the sigmoid colon due to enteritis. He also had myocardial infarction. Finally, he died of intestinal bleeding. Here, we describe this case with rare, multiple, consecutive manifestations of IgG4-RD, some of which might be caused by IgG4-related IAAA or side effects of treatments rather than by IgG4-RD itself. We report this case because the clinical course seemed rare for IgG4-RD or IgG4-related IAAA. For treating IgG4-RD with IgG4-related IAAA, we should consider factors causing the symptoms and carefully select the proper treatment.

Chronic Periaortitis: an Update.

We aim to review traditional concepts and recent developments on the nosology, pathophysiology, clinical phenotypes and treatment of chronic periaortitis (CP). CP is a rare disorder hallmarked by a periaortic fibro-inflammatory tissue. It can present as an isolated disease, but it can also be associated with other autoimmune and fibro-inflammatory lesions (e.g., fibrosing mediastinitis, sclerosing pancreato-cholangitis) that are part of the spectrum of IgG4-related disease. In a subgroup of patients, it also involves the thoracic aorta (so-called "diffuse periaortitis"), which supports the notion of an inflammatory disorder of large arteries. The pathogenesis of CP is multifactorial: recent studies have elucidated the predisposing role of immunogenetic variants and exposures to environmental agents such as smoking and asbestos. CP is a rare immune-mediated disease that affects the abdominal aorta and the iliac arteries and, in some cases, the thoracic aorta. It may overlap with manifestations of IgG4-related disease, and its treatment comprises glucocorticoids, conventional and biological immunosuppressive agents.

Immunoglobulin G4 Sclerosing Cholangitis: An Unusual Cause of Obstructive Jaundice—Case Report and Literature Review

IgG4-related sclerosing cholangitis (IgG4-SC) is one of the most common extra-pancreatic manifestation of IgG4-related disease (IgG4-RD) and is clinically distinct from primary sclerosing cholangitis (PSC). IgG4-RD is an increasingly recognized immune-mediated fibroinflammatory systemic disease, mostly affecting middle-aged and older male populations that can affect multiple organs. The presence of extra-biliary clinical manifestations of IgG4-RD, such as parotid and lacrimal swelling, lymphadenopathy, autoimmune pancreatitis, and retroperitoneal fibrosis, if present could provide important clues to diagnosis. High serum IgG4 levels, characteristic radiological (e.g., sausage-shaped pancreas or periaortitis) or biopsy findings (high percentage of IgG4+ plasma cells, lymphoplasmacytic infiltrate, storiform fibrosis, or obliterative phlebitis) in the setting of these features is diagnostic of this disease process. However, isolated IgG4-SC might be a diagnostic challenge, and the distinction is important as management of this disorder is vastly different from other causes of cholangitis such as PSC. Systemic corticosteroid therapy is the mainstay of therapy.

Laminin 511 is a target antigen in autoimmune pancreatitis.

Autoimmune pancreatitis (AIP), a major manifestation of immunoglobulin G4-related disease (IgG4-RD), is an immune-mediated disorder, but the target autoantigens are still unknown. We previously reported that IgG in patients with AIP induces pancreatic injuries in mice by binding the extracellular matrix (ECM). In the current study, we identified an autoantibody against laminin 511-E8, a truncated laminin 511, one of the ECM proteins, in patients with AIP. Anti-laminin 511-E8 IgG was present in 26 of 51 AIP patients (51.0%), but only in 2 of 122 controls (1.6%), by enzyme-linked immunosorbent assay. Because truncated forms of other laminin family members in other organs have been reported, we confirmed that truncated forms of laminin 511 also exist in human and mouse pancreas. Histologic studies with patient pancreatic tissues showed colocalization of patient IgG and laminin 511. Immunization of mice with human laminin 511-E8 induced antibodies and pancreatic injury, fulfilling the pathologic criteria for human AIP. Four of 25 AIP patients without laminin 511-E8 antibodies had antibodies against integrin α6β1, a laminin 511 ligand. AIP patients with laminin 511-E8 antibodies exhibited distinctive clinical features, as the frequencies of malignancies or allergic diseases were significantly lower in patients with laminin 511-E8 antibodies than in those without. The discovery of these autoantibodies should aid in the understanding of AIP pathophysiology and possibly improve the diagnosis of AIP.

IgG4-associated cholangitis - clinical presentation of an overlooked disease entity

IgG4-associated cholangitis (IAC) is the hepatobiliary manifestation of immunoglobulin G4-related disease, which is an immune-mediated fibroinflammatory systemic disorder characterised by often elevated IgG4 serum levels and typical histopathological findings in affected tissues. IAC is frequently (>90%) accompanied by autoimmune pancreatitis type1 (AIP), which is the pancreatic manifestation of immunoglobulin G4-related disease. In 80-85% of the cases patients with IAC are male, above 50years of age and present with jaundice and weight loss. Aremarkable percentage of patients with IAC has ahistory of long-term exposure to solvents, oil products and other organic agents representing so-called "blue-collar workers". Clinical features and imaging (i. e. strictures or mass-forming lesions in the biliary tract) may mimic other biliary diseases, such as primary or secondary sclerosing cholangitis and cholangiocarinoma. The HISORt criteria are used for diagnosing IAC and comprise histologic and imaging findings, serum IgG4, organ manifestation pattern and response to immunosuppressive therapy. Serum IgG4 levels are of diagnostic value when it is above 4times the upper limit of normal. Determination of the blood IgG4/IgG mRNA ratio using quantitative polymerase chain reaction (qPCR) is an accurate diagnostic tool currently under clinical validation. The majority of patients show an excellent response to corticosteroid therapy. Symptom recurrence, however, is common making long-term treatment with low-dose prednisolone and/or azathioprine frequently necessary.

Hypothyroidism in patients with autoimmune pancreatitis.

AIMTo examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis (AIP) patients.METHODSWe examined thyroid function in 77 patients with type 1 AIP (50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined.RESULTSEight patients (10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine (FT4) and high thyroid stimulating hormone (TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine (FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG4-related disease (IgG4-RD); presence of anti-thyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP.CONCLUSIONHypothyroidism was observed in 8 (10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.

An unusual manifestation of IgG4-related disease

An unusual manifestation of IgG4-related disease

Exophthalmos in a young woman with no Graves\u2019 disease \u2013 a case report of IgG4-related orbitopathy

BackgroundImmunoglobulin G4-related disease (IgG4-rd) is characterized by lymphoplasmacytic infiltration and tissue fibrosis. Orbital manifestations of IgG4-rd may include unilateral or bilateral proptosis, cicatricial extraocular muscle myopathy, orbital inflammation and pain which may mimic ophthalmic Graves’ disease.Case presentationA 25-year-old woman has been referred to the endocrinology clinic, 4 months after delivery, with suspected Graves’ orbitopathy. She has had bronchial asthma and recurrent skin rashes of unknown aetiology for the last 10 years and was treated for dacryoadenitis with steroid containing eye drops 5 years ago. During pregnancy she developed eyelid swelling. After delivery, eyelid redness and retrobulbar pain evolved. Proptosis was demonstrated by Hertel’s exophthalmometry. Orbital magnetic resonance imaging showed enlarged lateral and superior rectus muscles in both orbits. Thyroid function tests were in the normal range and no thyroid stimulating hormone (TSH) receptor autoantibodies were present. The eye muscle involvement pattern raised suspicion, and the high IgG4 level with positive histology of the lacrimal gland confirmed the diagnosis of immunoglobulin G4-related orbitopathy. Rapid improvement was observed following oral methylprednisolone.ConclusionsIgG4-related orbitopathy may mimic Graves’ orbitopathy. Euthyroid patients with no TSH receptor autoantibodies should be evaluated for immunoglobulin G4-related orbitopathy. Once IgG4-related orbitopathy is proven, other manifestations of IgG4-related disease have to be searched for; lifelong follow-up is warranted.

Manifestations of IgG4-related disease in otolaryngology

Manifestations of IgG4-related disease in otolaryngology

Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey.

Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. Overall, the IgG4 counts (87-345/high-power field) and IgG4/IgG-positive ratio were high (44-115%). The demographic findings included advanced age among the patients (55-80years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.

Pulmonary Inflammatory Pseudotumor and Skull Plasma Cell Granuloma as Metachronous Manifestations of IgG4-Related Disease

SESSION TITLE: Lung Pathology 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: IgG4 related disease is a recently identified entity that causes tumefactive lesions of organs due to lymphoplasmacytic infiltration by IgG4 positive plasma cells and leads to fibrosis. We present a young man with history of recurrent cryptogenic organizing pneumonia (COP) diagnosed retrospectively as inflammatory pseudotumor of the lung, after calvarial and meningeal plasma cell granuloma (PCG) diagnosis, both metachronous manifestations of IgG4 related disease. CASE PRESENTATION: A 28-year-old male presented to our hospital with seizures in 2016. MRI showed parietal and occipital calvarial lesions with meningeal enhancement that were resected. Biopsy showed spindle cell proliferation with mature polyclonal plasma cells and absence of ALK1 staining, consistent with PCG. IgG4 staining was positive. Computerized tomographic scan revealed chronic interstitial fibrotic changes in bilateral lung apices. On retrospective chart review, it was noted that he had presented with cough with interstitial infiltrates/fibrosis, fever and leukocytosis in 2014. At that time, an extensive infectious and connective tissue disease work up was negative and bone marrow aspiration and biopsy were normal. He was empirically treated with prednisone with subsequent resolution of symptoms. Earlier in 2009, he had presented to another hospital with fever and interstitial lung infiltrates and was treated as COP after lung biopsy. Reevaluation of the slides from 2009 biopsy was consistent with inflammatory pseudotumor of the organizing pneumonia, fibrohistiocytic type with predominant macrophages and fibrosis. DISCUSSION: Autoimmune pancreatitis was the first IgG4 disease to be characterized; however it can involve any organ. Organ involvement can be metachronous. Histopathological features of IgG4 related disease are dense lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis. There is variability in findings in organs such as the lungs in which aggregates of neutrophils may be found within inflammatory infiltrates, with lack of storiform fibrosis in non-solid lesions such as interstitial pneumonia. Steroids are the first line of treatment, however patients may flare despite adequate treatment. Immunosuppressive drugs have been used as steroid-sparing agents and for maintenance therapy. Steroid-refractory disease and recurrent disease has been shown to have a good response to rituximab. Response to treatment is better during the lymphoplasmacytic infiltration stage, prior to extensive fibrosis. CONCLUSIONS: It is important to consider IgG4 related disease in tumors of any organ and if tissue biopsy is consistent with this diagnosis, extensive surgery can be avoided since the disease in the active phase responds to steroid or rituximab. Reference #1: “Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations.” Am J Clin Pathol 94(5): 538-546. DISCLOSURE: The following authors have nothing to disclose: Aditya Kotecha, Hussein Saleh, Saraschandra Vallabhajosyula, Christina Desousa, AbuFazl Mohammed, Vivek Iyer, Geetha Krishnamoorthy No Product/Research Disclosure Information

Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis

IgG4-related disease (IgG4-RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG4 and tissue IgG4 levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid...

Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34mm/h; P=0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P=0.08). sIgG4 also correlated with ESR (ρ=0.26; P=0.05) and serum creatinine (SC) (ρ=0.26; P=0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P<0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P=0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P=0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P<0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

No definite clinical features of immunoglobulin G4–related disease in patients with pulmonary nodular lymphoid hyperplasia

Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells.