Serum Immunoglobulin G Levels Research Articles

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH. Presentation: 6/1/2024

Bullous Pemphigoid Severity and Levels of Antibodies to BP180 and BP230

The correlation between serum levels of autoantibodies against bullous pemphigoid (BP) antigens 180 (BP180) and 230 (BP230) with BP disease severity is unclear. To investigate the correlation of anti-BP180 and anti-BP230 immunoglobulin G (IgG) antibody levels with BP disease severity. A search was performed of the Cochrane Central Register of Controlled Trials, Embase, and PubMed databases from their respective inception to April 11, 2024. Studies evaluating the correlation between serum levels of anti-BP180 or anti-BP230 IgG measured using enzyme-linked immunosorbent assay (ELISA) and disease severity assessed per the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) or BP Disease Area Index (BPDAI) were included. No language or geographic restrictions were imposed. Nearly 0.4% of initially identified studies met the selection criteria. One researcher extracted data and another researcher confirmed data. The risk of bias was independently assessed by these researchers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, with discrepancies resolved by discussion with a third researcher. A random-effects model meta-analysis and a subgroup analysis were conducted based on the ELISA kit manufacturers. Pooled correlation coefficients of antibody levels with ABSIS and BPDAI. In all, 14 studies with 1226 participants were analyzed. The risk of bias of included studies was generally low. The meta-analysis found anti-BP180 autoantibody levels showed moderate correlation with objective BPDAI (r = 0.56; 95% CI, 0.46-0.64) at baseline, strong correlation (r = 0.63; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. Anti-BP180 autoantibody levels also showed moderate correlation (r = 0.52; 95% CI, 0.39-0.62) with ABSIS at baseline, strong correlation (r = 0.62; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. By contrast, anti-BP230 autoantibody levels showed no association with objective BPDAI and ABSIS at diagnosis and follow-up. The subgroup analysis found similar results when using different ELISA kits. The findings of this systematic review and meta-analysis indicated that anti-BP180 autoantibody levels may serve as an adjunctive tool for monitoring BP disease severity and guiding clinical care for patients with BP.

Immunomodulatory and anti-inflammatory properties of immunoglobulin G antibodies.

Antibodies provide an essential layer of protection from infection and reinfection with microbial pathogens. An impaired ability to produce antibodies results in immunodeficiency and necessitates the constant substitution with pooled serum antibodies from healthy donors. Among the five antibody isotypes in humans and mice, immunoglobulin G (IgG) antibodies are the most potent anti-microbial antibody isotype due to their long half-life, their ability to penetrate almost all tissues and due to their ability to trigger a wide variety of effector functions. Of note, individuals suffering from IgG deficiency frequently produce self-reactive antibodies, suggesting that a normal serum IgG level also may contribute to maintaining self-tolerance. Indeed, the substitution of immunodeficient patients with pooled serum IgG fractions from healthy donors, also referred to as intravenous immunoglobulin G (IVIg) therapy, not only protects the patient from infection but also diminishes autoantibody induced pathology, providing more direct evidence that IgG antibodies play an active role in maintaining tolerance during the steady state and during resolution of inflammation. The aim of this review is to discuss different conceptual models that may explain how serum IgG or IVIg can contribute to maintaining a balanced immune response. We will focus on pathways depending on the IgG fragment crystallizable (Fc) as pre-clinical data in various mouse model systems as well as human clinical data have demonstrated that the IgG Fc-domain recapitulates the ability of intact IVIg with respect to its ability to trigger resolution of inflammation. We will further discuss how the findings already have or are in the process of being translated to novel therapeutic approaches to substitute IVIg in treating autoimmune inflammation.

Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1.

Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428). IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this.

Factors related to elevated serum immunoglobulin G4 (IgG4) levels in a Japanese general population

BackgroundElevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population.MethodsSerum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations.ResultsThe mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis.ConclusionsElevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.

Pricking-cupping combined with auricular thumbtack needle for postherpetic neuralgia of qi stagnation and blood stasis on chest and waist: a randomized controlled trial

To observe the clinical effect of pricking-cupping combined with auricular thumbtack needle for postherpetic neuralgia (PHN) of qi stagnation and blood stasis on chest and waist. A total of 98 patients with PHN of qi stagnation and blood stasis on chest and waist were randomized into an observation group (49 cases, 1 case was eliminated, 1 case dropped out) and a control group (49 cases, 1 case dropped out). In the observation group, treatment of pricking-cupping combined with auricular thumbtack needle was delivered, pricking and cupping were applied at Jiaji points (EX-B 2) at the related spinal segments corresponding to the pain sites and regional ashi points, once every other day, auricular thumbtack needle was applied at Xin (CO15), Shenmen (TF4), Neifenmi (CO18), Pizhixia (AT4), etc., once every 3 days. In the control group, pregabalin capsule was taken orally, 75 mg a time, twice a day. The treatment of 4 weeks was required in the two groups. Before and after treatment, the scores of TCM symptom, visual analogue scale (VAS), Pittsburgh sleep quality index (PSQI), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were observed, the serum levels of immunoglobulin G (IgG), interleukin-6 (IL-6), C-reactive protein (CRP) were detected, and the clinical efficacy and safety were evaluated in the two groups. After treatment, the item scores and total scores of TCM symptom, as well as the scores of VAS, PSQI, SDS and SAS were decreased compared with those before treatment (P<0.05); the item scores of pruritus degree, tactile sensitivity, skin numbness and total score of TCM symptom, as well as the scores of VAS, PSQI, SDS and SAS in the observation group were lower than those in the control group (P<0.05). After treatment, the serum levels of IgG were increased (P<0.05), while the serum levels of IL-6 and CRP were decreased (P<0.05) compared with those before treatment in the two groups; in the observation group, the serum level of IgG was higher (P<0.05), while the serum levels of IL-6 and CRP were lower (P<0.05) than those in the control group. The total effective rate was 95.7% (45/47) in the observation group, which was superior to 77.1% (37/48) in the control group (P<0.05). The incidence rate of adverse reaction was 6.4% (3/47) in the observation group, which was lower than 12.5% (6/48) in the control group (P<0.05). Pricking-cupping combined with auricular thumbtack needle can effectively relieve the clinical symptoms in patients with PHN of qi stagnation and blood stasis on chest and waist, reduce the pigmentation of herpes and improve itch or burning, numb sensations in the skin lesions, improve the sleep quality and relieve anxiety and depression.

Umbilical cord blood as a substitute for neonatal blood in measuring serum albumin and immunoglobulin G levels.

In this study, we investigated the clinical feasibility of using umbilical cord blood as an alternative to neonatal blood for measuring serum albumin and immunoglobulin G (IgG) levels in newborns, including preterm newborns. Serum levels of albumin and IgG were measured in cord and neonatal blood from singleton newborns. We analyzed correlations and systematic errors between cord and neonatal blood measurements, stratifying the results for very preterm newborns (VPNs) born at a gestational age of less than 32 weeks and non-VPNs born at a gestational age of 32 weeks or later. Among all 494 newborns (78 VPNs and 416 non-VPNs), serum albumin and IgG levels were determined for 95.7% and 88.7% of them, respectively. Strong correlations between cord and neonatal blood were observed for the serum albumin and IgG levels (rs = 0.864 and 0.966, respectively). Moreover, the measurement errors between cord and neonatal blood were small for all newborns (0.2g/dL and 65mg/dL, respectively). These findings were consistent with both VPNs and non-VPNs. Umbilical cord blood is a suitable substitute for neonatal blood in measuring serum albumin and IgG levels in newborns, even in premature newborns.

The effects of Bacillus subtilis spores and yeast cell wall supplementation on growth and health in Holstein dairy calves

The study aimed to assess the impact of Bacillus subtilis spores and yeast cell wall (YCW) on the performance and health of dairy calves during the milk-feeding period. Thirty female Holstein calves (birth body weight [BW] of 36.7 ± 4.81 kg) were randomly assigned to three treatments: Control (CTL, no additives), T1 (Bacillus subtilis spores), and T2 (Bacillus subtilis + YCW). Animals were individually housed with free access to water and commercial pellet starter. Calves received 8 L/d of pasteurized waste milk and were weaned at 63 d of age. The treatments (T1 and T2) were mixed into milk and administered daily from 3 to 63 d of age. Dry matter (DM) intake (from liquid and starter feed), fecal score, and rectal temperature were recorded daily. Additionally, heart girth was measured at 0, 15, 30, 45, and 60 d of age, and BW was measured at 0 and 60 d of age. Blood was sampled from the jugular vein at 0, 20, and 60 d of age for analysis of serum immunoglobulin G (IgG). There was treatment × time interaction (P = 0.04) for fecal consistency scores. Calves supplemented with Bacillus subtilis tended (χ2 test, P = 0.07) to have lower cases of diarrhea than other groups. T1 or T2 supplementations did not affect milk DM intake, starter DM intake, or total DM intake. Growth performance (BW at weaning and average daily gain) was similar between treatments. Dairy calves fed Bacillus subtilis plus YCW tended to have (P = 0.09) higher rectal temperature and had higher frequency (χ2 test, P < 0.01) of rectal temperature >39.1°C compared to the CTL and Bacillus subtilis groups. However, treatments had similar levels of serum IgG (CTL = 18.3, T1 = 16.7, and T2 = 18.6 mg/mL; P = 0.58). Our results suggest that Bacillus subtills and YCW may interact in the digestive tract of young calves as evidenced by the increased rectal temperature in T2. While the cause of this interaction remains uncertain, there was no negative effect on the animal health or growth performance. The use of Bacillus subtilis spores shows promise in improving fecal consistency scoring in dairy calves fed pasteurized waste milk during the pre-weaning phase.

Immunoglobulin therapies for primary immunodeficiency diseases (part 2): considerations for dosing strategies.

Immunoglobulin G (IgG) dosing in treating primary immunodeficiency diseases (PIDs) is individualized, which often involves regular monitoring of IgG levels, and considers patient experiences with immunoglobulin therapies, their clinical status and physician judgment. The frequency and dose(s) of intravenously (IVIG) and subcutaneously (SCIG) administered IgGs (including hyaluronidase-facilitated SCIG) requirerigorous evaluation to maximize therapeutic benefits. Monitoring serum IgG levels represents an integral part of diagnosing primary immunodeficiency diseases and determining or adjusting IgG dosing strategies to meet individual patient needs, but cannot be conducted in isolation. This review discusses the current state and future perspectives on dosing strategies for different types of IgG therapies, as well as dosing considerations for specific patient populations, immunoglobulin-naive patients and patients switching between IVIG and SCIG.

Quantity and Quality of Naturally Acquired Antibody Immunity to the Pneumococcal Proteome Throughout Life.

Young children and older adults are susceptible for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Pneumococcal protein-specific antibodies play a protective role against IPD; however, not much is known about the pace of acquisition, maturation, and maintenance of these antibodies throughout life. Immunoglobulin G (IgG) and IgA levels, avidity, and/or specificity to the pneumococcal proteome in serum and saliva from healthy young children, adults, and older adults, with known carriage status, were measured by enzyme-linked immunosorbent assay (ELISA) and 2-dimensional western blotting against ΔcpsTIGR4. Eleven-month-old children, the youngest age group tested, had the lowest pneumococcal proteome-specific IgG and IgA levels and avidity in serum and saliva, followed by 24-month-old children and were further elevated in adult groups. Among adult groups, the parents had the highest serum and saliva IgG and IgA antibody levels. In children, antibody levels and avidity correlated with daycare attendance and presence of siblings, posing as proxy for exposure and immunization. Immunodominance patterns slightly varied throughout life. Humoral immunity against the pneumococcal proteome is acquired through multiple episodes of pneumococcal exposure. Low-level and low-avidity antiproteome antibody profiles in young children may contribute to their IPD susceptibility, while in overall antiproteome antibody-proficient older adults other factors likely play a role.

Clinicopathological features of immunoglobulin G4-related constrictive pericarditis

AimConstrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. MethodsAmong 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. ResultsCompared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. ConclusionsPericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study.

The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Forty healthy volunteers (age: 35-60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers' cellular and humoral immune functions. In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

Salivary IgG and IgA in newborn calves and the possible role in the assessment of passive immunity transfer.

The transfer of immunoglobulins from the mother to newborns is widely recognized as a critical event for safeguarding offspring against potentially life-threatening infectious diseases. Mainly for this reason, this study aimed to assess the concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in the saliva of newborn calves and explore its potential use for monitoring passive immunity transfer from cows to calves, as also to evaluate how colostrum intake affects serum and saliva IgG and IgA concentrations. The quality of colostrum samples was evaluated using an optical refractometer before administration to the calves. Saliva and blood samples from 24 calves were obtained at the day of birth (T0) and 2 days after (T2) for determination of serum concentrations of total protein by refractometer, IgG and IgA (both on serum and saliva) by ELISA test. Positive correlations were observed between salivary IgA at T2 and salivary IgG at T2. A significant increase in both IgG and IgA levels in calf serum and saliva was noted. Salivary IgA levels can reflect salivary IgG levels. These findings suggest the potential utility of IgA in monitoring passive immunity transfer, and do not exclude saliva as an alternative, practical, and non-invasive matrix for assessing passive immunity transfer.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

CORONARY ARTERY ANEURYSM IN IGG4–RELATED DISEASE

Abstract Introduction Coronary artery ectasia is a rare disease defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adiacent normal segment. The etiology is diverse and can be rarely associated with immunoglobulin G4 (IgG4)–related disease. The high levels of serum IgG4 may promote the development of low–density plaques, intimal thickening due to pericoronitis and subsequent coronary ectasia. Case Report We present the case of a 72–year–old male patient with arterial hypertension, dyslipidemia, chronic renal insufficiency, and a family history of cardiovascular diseases. In the previous year, he suffered a cerebral hemorrhage attributed to an unspecified cerebral vascular malformation, which was managed with an endovascular approach. The patient was admitted for Non–ST–segment Elevation Myocardial Infarction (NSTEMI). Coronary angiography revealed widespread ectasia of the coronary vessels, a chronically occluded marginal branch, and an aneurysmatic proximal right coronary artery with the presence of a thrombus on the aneurysmal segment, dissolved following administration of intracoronaric heparin. Furthermore a critical stenosis at the crux involving the posterior interventricular branch was detected and angioplasty with drug–eluting stent implantation was performed on the affected vessel. Given the coronary artery ectasia, aortic ectasia revealed by echocardiography, renal insufficiency and persistently elevated amylase and lipase levels, further diagnostic investigation was conducted suspecting IgG4–related disease. Hematological tests revealed elevated IgG and IgG4 subclass levels (882 mg/dL and 1438 mg/L, respectively), C3 117 mg/dL, C4 30 mg/dL, and total IgE 130 KU/L. The diagnosis of IgG4–related disease was confirmed and the patient was advised to continue cardiological and rheumatological follow–up. Conclusion When the coronary arteries are involved in the IgG4–related disease, risk of acute events such as heart attack may increase and the prognosis is poor. Coronary thickening and ectasia, typical imaging features, other aortic involvement and inflammation indicators, like elevated serum IgG4, should be considered as red flags for an early investigation and subsequent early intervention.

Does the SARS-CoV-2 mRNA vaccine and its serum IgG levels affect fertility treatments and obstetric outcomes? An observational cohort study

BackgroundAlthough there are some data regarding the COVID-19 vaccine and in in vitro fertilization (IVF) treatments, its potential impact in terms of serum immunoglobulin G (IgG) levels has not been evaluated prospectively. This study aimed to assess the effect of COVID-19 vaccine and IgG levels on IVF outcomes.MethodsThis observational, cohort study was conducted at a referral IVF unit. Couples undergoing IVF treatment during the COVID-19 vaccination period were recruited from March–April 2021. The study compared 38 women who had received the Pfizer mRNA COVID-19 vaccination to 10 women who had not and were not infected by the virus. We also compared pre- and post-vaccination IVF treatments for 24 women. The relation between serologic titers and IVF treatment outcomes was also assessed.ResultsNo significant difference was found between the vaccinated and unvaccinated/uninfected groups regarding the main outcome measures. However, there was a trend toward a higher pregnancy rate for the unvaccinated group (57% vs. 23%, p = 0.078) but no difference in delivery rate (p = 0.236), gestational week (p = 0.537) or birth rate (p = 0.671).ConclusionWe cautiously state that the COVID-19 mRNA vaccine does not affect fertility outcomes, including fertilization, pregnancy and delivery rates, obstetric outcomes, and semen parameters, regardless of measured IgG levels.

Association between serum IgG concentrations and the incidence of infections in patients with chronic lymphocytic leukemia and secondary immunodeficiency under treatment with Privigen.

To investigate the association between serum immunoglobulin G (IgG) concentrations and the incidence of infections in patients with chronic lymphocytic leukemia (CLL) and secondary immunodeficiency receiving treatment with Privigen. Data was analyzed from a non-interventional study conducted in 31 centers in Germany and 1 in Austria. Adult CLL patients with hypogammaglobulinemia and recurrent infections were allowed to enter the study upon signing informed consent, if a prior decision for treatment with Privigen had been made. All infections requiring an antimicrobial treatment were subject to analysis. Patients were stratified according to their mean post-baseline serum IgG trough levels in a group with lower IgG trough levels (≤ 5.0 g/L), and a group with higher IgG trough levels (> 5.0 g/L). Overall, 89 patients and 840 treatment cycles were analyzed. Up to 11 treatment cycles (average duration 29 days) were documented in each patient. In the group with higher IgG trough levels (> 5.0 g/L, N = 72), significantly fewer infections were observed than in the group with lower IgG trough levels (≤ 5.0 g/L, N = 17), including fewer severe and serious infections. The Privigen dosage was a major determinant of the post-baseline serum IgG levels. Overall tolerability of Privigen was assessed as very good or good in 91% of patients. This analysis confirms the association of serum IgG trough levels with the incidence of infections and highlights the importance of careful monitoring of IgG levels during treatment of secondary immunodeficiencies in CLL patients.

Imaging of Common and Uncommon Manifestations of Immunoglobulin G4‐Related Disease in the Head and Neck

Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic immune-mediated disease, encompassing several conditions previously thought to be unrelated, which can mimic malignant, infectious, and inflammatory disorders. Head and neck IgG4-RD most frequently affects the salivary glands and orbit; however, it can involve virtually any subsite. Diagnosis is challenging and relies on the clinical presentation, serum immunoglobulin G4 levels, and histopathology. Although imaging is nonspecific, growing knowledge of IgG4-RD allows characterization of imaging patterns and description of novel findings. This review focuses on cross-sectional imaging findings of extracranial IgG4-RD in the head and neck, presenting cases in frequent and unusual subsites, with some cases with few descriptions in the radiological literature, such as the pharynx and larynx, temporal bone, paranasal sinuses, and perivascular areas.Learning Objective: To describe the imaging findings of IgG4-RD in the head and neck to suggest the diagnosis and identify the involvement of common and uncommon subsites.

Autoimmune pancreatitis: Cornerstones and future perspectives.

Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.