Elevated IgG Research Articles

Laboratory characteristics of IgG4-related disease: A retrospective study from a single tertiary medical center.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with unique histopathological features that can affect most organs, making diagnosis challenging. This study characterized detailed laboratory characteristics of IgG4-RD. Baseline clinical and laboratory features of 33 patients with IgG4-RD were reviewed, including serum IgG4 concentrations, serum free light chains (sFLCs), IgGĸ- and IgGλ-heavy/light chains (HLCs), capillary serum protein electrophoresis (SPE), and immunofixation electrophoresis (IFE) of IgG4 subclass. The cohort of 33 patients showed male predominance (94%), with 8 (24%) exhibiting multiple organ involvement. Most patients (88%) had an elevated IgG4 concentration, and 67% had elevated erythrocyte sedimentation rate and IgE levels. Median IgG4 concentration at baseline was significantly higher in patients with >2 organs involved than those with ≤2. Furthermore, erythrocyte sedimentation rate was significantly correlated with serum IgG4 concentrations at baseline. SPE results demonstrated polyclonal gammopathy in most patients. Half of the patients had an increased κ/λ sFLC ratio, 42% had an increased IgGκ/IgGλ HLC ratio. Most patients exhibited hypergammaglobulinemia in the anodal end of the ɤ region on SPE. This study describes detailed laboratory features of IgG4-RD. Although none of these tests are considered diagnostically sufficient by itself, the provided laboratory characteristics can increase awareness of this disorder and help distinguish it from other IgG4-RD mimics.

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease.

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.

Prevalence of high affinity naturally occurring IgG2 antibodies against human chorionic gonadotropin and its subunits in patients with ovarian cyst

Naturally occurring antibodies to tumour antigens are gaining interest as clinically important cancer biomarkers for early diagnosis, prognosis and for the development of anti-cancer therapeutics. The glycoprotein αβ heterodimer hormone human chorionic gonadotropin (hCG) and its β subunit (hCGβ) are produced by various cancers, and their increased serum levels correlate with poor prognosis. We have previously reported that patients with benign ovarian cysts, but not the malignant tumours, were characterized by augmented serum levels of naturally-occurring IgG antibodies to hCG and hCGβ. Here we further characterise these antibodies in patients with ovarian cysts.IgG and IgM antibody binding to whole hCG, hCGβ, hCGα, hCGβ C-terminal peptide (hCGβCTP), and the hCGβ core fragment (hCGβCF) were measured in the sera from 36 patients with ovarian cysts and 12 healthy non-pregnant women using a standard ELISA. IgG subclass usage and affinity was also determined together with cross-binding to whole hCG and its subunits of four selected commercial monoclonal antibodies generated against ovarian cyst mucins.Our results showed that 91.7% of the sera tested contained elevated IgG, but not IgM antibodies to one or several antigens, with an overwhelming prevalence of high affinity IgG2 indicating their binding to carbohydrate epitopes and possibly ovarian cyst mucins. Anti-mucin commercial antibody ab212418 (Abcam) produced against Gal1-3GalNAc, exhibited strong cross-binding to hCGαβ, hCGβ, hCGα and hCGβCTP. The protective anti-cancer potential of these antibodies will be further investigated and could lead to the development of novel treatment strategies for ovarian cancer.

Activation of SARS-CoV-2 neutralizing antibody is slower than elevation of spike-specific IgG, IgM, and nucleocapsid-specific IgG antibodies

COVID-19 antibody testing has been developed to investigate humoral immune response in SARS-CoV-2 infection. To assess the serological dynamics and neutralizing potency following SARS-CoV-2 infection, we investigated the neutralizing (NT) antibody, anti-spike, and anti-nucleocapsid antibodies responses using a total of 168 samples obtained from 68 SARS-CoV-2 infected patients. Antibodies were measured using an authentic virus neutralization assay, the high-throughput laboratory measurements of the Abbott Alinity quantitative anti-spike receptor-binding domain IgG (S-IgG), semiquantitative anti-spike IgM (S-IgM), and anti-nucleocapsid IgG (N-IgG) assays. The quantitative measurement of S-IgG antibodies was well correlated with the neutralizing activity detected by the neutralization assay (r = 0.8943, p < 0.0001). However, the kinetics of the SARS-CoV-2 NT antibody in severe cases were slower than that of anti-S and anti-N specific antibodies. These findings indicate a limitation of using the S-IgG antibody titer, detected by the chemiluminescent immunoassay, as a direct quantitative marker of neutralizing activity capacity. Antibody testing should be carefully interpreted when utilized as a marker for serological responses to facilitate diagnostic, therapeutic, and prophylactic interventions.

A case of hilar biliary cystadenoma with elevated IgG4 levels.

Cholangiocytic adenoma in the hilar bile duct is rare, and elevated IgG4 at the same time is extremely rare. This situation has not been reported in the literature. Nonetheless, the current case involved hilar biliary cystadenoma with elevated IgG4 levels. A 66-year-old man presented at this hospital with dark tea-colored urine. Preoperative imaging studies suggested hilar cholangiocarcinoma. This case demonstrates the difficulty of preoperative diagnosis of benign hilar lesions and the rarity of two combined benign lesions. A point of contention is whether this case should be treated with surgery or hormone therapy.

Clinical Characteristics and Potential Mechanisms in Patients with Abnormal Liver Function Indices and Elevated Serum IgG4.

We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.

Evaluation of SARS-CoV-2 Serum Level in Patients Vaccinated With Sinopharm/BBIBP-CorV With Kidney Transplantation

BackgroundEvery year, a large number of people undergo kidney transplants because of various reasons leading to renal failure. These patients usually have low immunoglobulin levels due to the use of immunosuppressive drugs. In recent years, the COVID-19 pandemic has been a major global health risk. Patients who are immunocompromised or who have diabetes are especially at risk.MethodsIn this study, we enrolled 156 patients who had undergone kidney transplant and had received 2 doses of Sinopharm/BIBP-CorV. The serum antibody levels against COVID-19 spike glycoprotein (immunoglobulin [Ig] G and IgM) were measured using a sandwich enzyme-linked immunosorbent assay kit to evaluate whether different immunosuppressive drugs could affect the body's response to the said vaccine.ResultsWe found that only patients receiving Rapamune had increased IgM secondary to COVID-19 vaccine. None of the immunosuppressive drugs in this study have shown a positive correlation with increased IgG levels. The only factor that showed a significant effect on both IgM and IgG was a positive history of COVID-19, which was correlated with increased levels of serum IgG/M.ConclusionsOnly patients treated with Rapamune showed an acute immune reaction to the vaccine in the form of positive serum IgM levels, and no rise of serum IgM antibody was observed in COVID-19-naive patients. Patients who had a previous history of COVID-19 infection showed an elevated serum IgM and IgG level, suggesting that vaccines in general and Sinopharm/BIBP-CorV in particular are not enough to ensure immunity against COVID-19 in transplant recipients. We recommend further studies using different types of vaccines and immunosuppressive drugs.

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression.

The increased glycation of elastin is an important factor in vascular changes in diabetes. Using the ELISA method, we determined serum levels of IgM and IgG autoantibodies to advanced glycation end products of vascular elastin (anti-AGE EL IgM and anti-AGE EL IgG) in 59 hypertensive patients with type 2 diabetes (T2D) and 20 healthy controls. Serum levels of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and the C-reactive protein (CRP) were also determined. The levels of anti-AGE EL IgM antibodies in the T2D group were similar to those in the control group, while those of anti-AGE EL IgG antibodies were significantly higher (p = 0.017). Significant positive correlations were found between the levels of anti-AGE EL IgM antibodies and MMP-2 (r = 0.322; p = 0.013) and between the levels of anti-AGE EL IgG antibodies and CRP (r = 0.265; p = 0.042). Our study showed that elevated anti-AGE EL IgG antibody levels may be an indicator of the enhanced AGE-modification and inflammatory-mediated destruction of vascular elastin in hypertensive patients with T2D. Anti-AGE EL IgM antibodies may reflect changes in vascular MMP-2 activity, and their elevated levels may be a sign of early vascular damage.

The Human Filaria Loa loa: Update on Diagnostics and Immune Response.

Loa loa loiasis was considered an anecdotal disease 30 years ago. Its spread in Equatorial Africa and the side effects associated with mass drug administration programs against filariasis in co-endemic areas have drawn the attention of the international research community. Progress in research conducted to date has provided insight into the immunobiology of this parasite. An interesting finding reported in several studies is that 70% of individuals with loiasis do not carry microfilariae in their blood, and 30% are microfilaremic, suggesting the involvement of several immunological mechanisms, as shown by elevated specific IgG4 and IgE levels signifying a potential cross-linking mechanism between the two isotypes via L. loa antigen to prevent allergy. A mechanism of anergy in the appearance of microfilariae in the peripheral blood results in immunological unresponsiveness in individuals with microfilariae. There is an interaction between other pathogens (parasites, bacteria, viruses) in individuals co-infected with L. loa. The strong antigen cross-reactivity between L. loa and lymphatic filarial worms warrants a re-evaluation of the distribution of the latter in co-endemic regions. The mechanism of concomitant immunity observed in the elimination of microfilariae or infective larvae (third-stage larvae, L3) may be used for the conception of an immunoprophylactic strategy.

Multi-System Langerhans Cell Histiocytosis as a Mimic of IgG4-Related Disease: A Case Report and Literature Review

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the clonal accumulation and/or proliferation of specific dendritic cells resembling normal epidermal Langerhans cells (LCs). Clinical manifestations are variable, depending on the affected tissues or organs, however, LCH with elevated serum IgG4 has not been reported. Herein, we reported a 26-year-old Chinese female multi-system LCH (MS-LCH) who first presented with central diabetes insipidus (CDI), accompanied by panhypopituitarism and hepatic dysfunction. Diagnostic investigations were strongly suspicious of IgG4-RD because of elevated serum IgG4 levels during the process. Furtherly, thyroid and lymph node involvement and biopsy led to the diagnosis of MS-LCH; the strongly positive staining of CD1a, S100, CD207 (langerin), and Ki67 was found. Moreover, after systemic treatment with five cycles of chemotherapy, many lesions were greatly improved. Since both LCH and IgG4-RD are orphan diseases that can affect any organ, the differential diagnosis is challenging, especially when LCH is associated with unexplained serum IgG4 elevation. In this article, the case of a young woman suffering from MS-LCH that affected organs including the pituitary, thyroid, lymph node, and liver was summarized, and relevant literature was reviewed to better equip the diagnosis and treatment in its early stages.

Systemic sclerosis patients with negative antinuclear antibodies have distinctive clinical manifestations: amulticenter CRDC cohort in China.

The presence of circulating antinuclear antibodies (ANAs) is ahallmark of immune dysregulation in patients with systemic sclerosis (SSc). Avariety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in aChinese Rheumatism Data Center (CRDC) multicenter cohort in China. Patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs. Antinuclear antibodies were detected in 2129 of 2809patients enrolled in the study; 4.2% of patients were negative. There were more males among ANA-negative SSc patients (29/60 vs. 294/1746, p < 0.001). The incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs. 18.5%, p = 0.002), interstitial lung disease (65.2% vs. 77.9%, p = 0.015), and pulmonary arterial hypertension (11.5% vs. 29.0%, p = 0.006) was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal erythrocyte sedimentation rate (32.4% vs. 47.6%, p = 0.013) and IgG elevation (14.3% vs. 37.0%, p = 0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients. Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach

Malaria is a complex disease caused by parasites of the genus Plasmodium and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. Thus, a combination of different approaches is needed to control malaria. Resistance to first-line drugs and insecticides, on the other hand, makes the need for an effective vaccination more urgent than ever. Because erythrocyte parasites cause the most clinical symptoms, developing a vaccination for this stage of infection might be highly beneficial. In this research, we employed various bioinformatics methods to create an efficient multi-epitope vaccine that induces antibodies against the blood stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The B, HTL epitopes, and epitope conservation were predicted. The predicted epitopes (including 5 B and 5 HTL epitopes) were connected using suitable linkers, and the flagellin molecule was used as an adjuvant to improve its immunogenicity. The final construct vaccine with 414 amino acids long was designed. The vaccine's allergenicity, antigenicity, solubility, physicochemical characteristics, 2D and 3D structure modeling, molecular docking, molecular dynamics simulation, in silico cloning, and immunological simulation were tested. In silico immune simulation results showed significantly elevated IgG1 and IgM and T helper cells, INF γ, IL 2, and B-cell populations after the injection of the designed vaccine. These significant computational analyses indicated that our proposed vaccine candidate might activate suitable immune responses against malaria. However, in vitro and in vivo studies are essential for further validation.

Specificity of Immunoglobulin Response to Nontuberculous Mycobacteria Infection in People with Cystic Fibrosis.

ABSTRACTNontuberculous mycobacteria (NTM) infections are increasingly prevalent in chronic lung diseases, including cystic fibrosis (CF). Mycobacterium abscessus is of particular concern due to relatively greater virulence and intrinsic antimicrobial resistance. Airway culture identification, the standard method for detecting pulmonary infection, is hindered by low sensitivity, long culture times, and reliance on sputum production or lavage. A culture-independent test for detecting NTM infection could complement, or replace, sputum culture, which is becoming more difficult to obtain with reduced sputum production by people with CF (pwCF) on highly effective modulator therapy. We describe an assay for the detection of plasma anti-M. abscessus antibodies of pwCF to antigens from M. abscessus lysates. Anti-M. abscessus IgG and IgA, but not IgM, discriminated with high specificity subjects infected with M. abscessus from those infected by M. avium complex, and from those with distant or no NTM infections. The IgG3 subclass predominated with minor contributions by other subclasses. Both aqueous and organic soluble antigens were recognized by plasma IgG. A validation cohort measuring IgG and IgG3 identified M. abscessus positive subjects, and elevated IgG was sustained over several years. These studies show the benefit of M. abscessus cell lysates to detect plasma IgG of subjects with CF and M. abscessus infections. Subclass analysis suggests that IgG3 is the predominant subtype in these subjects with chronic bacterial infections suggesting a defect in class maturation. Serodiagnosis could be useful to monitor M. abscessus group infections in chronic lung disease as an adjunct or alternative to culture.IMPORTANCE Lung infections with nontuberculous mycobacteria (NTM), and particularly Mycobacterium abscessus, a pathogen with high antibiotic resistance, are of great concern due to poor clinical outcomes and challenging detection in people with cystic fibrosis and other diseases. Standard detection methods are insensitive and increasingly difficult. We describe the measurement of NTM-specific antibodies from plasma to identify subjects infected with M. abscessus. The assay is sensitive and provides information on the immune response to NTM infections. This assay could be used to help identify subjects with NTM pulmonary infections and track disease progression, either alone or in conjunction with other tests.

Preexisting Humoral Immunity Cross-Reacting with SARS-CoV-2 Might Prevent Death Due to COVID-19 in Critical Patients.

The preexistence of humoral immunity, which cross-reacts with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein due to prior endemic low-pathogenic human coronavirus infection, has been reported, but its role in coronavirus disease 2019 (COVID-19) outcomes remains elusive. We evaluated serum samples obtained from 368 patients before the pandemic and 1423 independent serum samples from patients during the pandemic. We found that approximately 6~13% and 1.5% of patients had IgG cross-reactivity to the SARS-CoV-2 spike and nucleocapsid proteins in both cohorts. We evaluated the IgG cross-reactivity to the SARS-CoV-2 spike and nucleocapsid proteins in 48 severe or critical COVID-19 patients to evaluate if the elevation of IgG was evoked as a primary response (IgG elevation from 10 days after antigen exposure) or boosted as a secondary response (IgG elevation immediately after antigen exposure). Approximately 50% of patients showed humoral immune responses to the nucleocapsid protein of SARS-CoV-2. Importantly, none of the critically ill patients with this humoral immunity died, whereas 40% of patients without this immunity did. Taken together, subjects had humoral immunity to SARS-CoV-2 nucleocapsid but not spike before the pandemic, which might prevent critically ill COVID-19 patients from dying.

THU471 - Isolated IgG elevation is not associated with worse outcome in patients with autoimmune hepatitis

THU471 - Isolated IgG elevation is not associated with worse outcome in patients with autoimmune hepatitis

Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder

BackgroundDown syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention.MethodsA retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms.ResultsIndividuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04–1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64–37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88–9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective.ConclusionsThis study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.

The Third dose of CoronVac vaccination induces broad and potent adaptive immune responses that recognize SARS-CoV-2 Delta and Omicron variants

ABSTRACT The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

Hyperphosphatemia: A Clue to Diagnosis

Serum phosphate level reference range in adults is 2.5 mg/dL to 4.5 mg/dL and in children is 3 mg/dL to 6 mg/dL. The causes of hyperphosphatemia fall into four categories. These are decreased renal excretion of phosphorus, exogenous phosphorus administration, redistribution of phosphorus, and pseudohyperphosphatemia. We report a 69-year-old gentleman presented with the history of swelling of feet and facial puffiness of 1 month duration. He had renal failure with normal sized kidneys. Serum phosphorus was high. Advanced investigations revealed plasma cell proliferative disorder (clonal bone marrow plasma cells &gt;10%) on bone marrow examination, presence of M band at the junction of beta-2 and gamma region, and elevated serum IgG and serum beta-2 microglobulin. Hyperphosphatemia in multiple myeloma may be true, or pseudohyperphosphatemia. Diligent history, examination, and investigations have yielded the possibility of pseudohyperphosphatemia owing to multiple myeloma in our patient. The interference with the phosphomolybdate ultraviolet assay for serum phosphorus estimation is one of the reasons of pseudohyperphosphatemia in multiple myeloma. The other mechanism of pseudohyperphosphatemia could be the direct binding of paraprotein to phosphorus.

Age-Related Dynamics of Serum Anti-Spike IgG Ab After the Third Dose of BNT162b2 Vaccine in a Naive Health Care Workers Population.

The kinetics of postvaccination serum anti-Spike IgG concentration were determined in 1,541 health care workers (Sant'Andrea Hospital of Rome, Italy) with no prior infection by SARS-COV-2. Anti-Spike IgG were measured at 3, 12, and 24 weeks after the completion of the primary vaccine cycle (two doses of the BNT162b2 vaccine by Biontech/Pfizer) and 3 weeks apart a third BNT162b2 dose. Stratification of the study population by age (decades from 21-30 to 61-70) highlighted that 24 weeks after cycle completion all age groups had an order of magnitude reduction in serum IgG titers. Considering older adults (age 61-70), they had significantly lower serum IgG titers at each time point compared with younger people, except after the booster dose, which induced similar and elevated IgG titers despite the age.