Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

BackgroundCurrently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy.ObjectiveTo determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult.MethodsThis is a prospective cohort study of adult aged 18–59 years who received 2-dose SV at 14–35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×10¹⁰ viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route.ResultsFrom August2021, 100 adults with median age of 46 years(IQR 41–52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7–26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4–125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2–96.8) at day14, 73.1% inhibition (66.7–80.2) at day90, and 22.7% inhibition (14.9–34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and ?37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9–2343.2) at day14 and 744.6 BAU/ml(650.1–852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83–1.20) at day14, and 0.82(0.66–1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister.ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.     

Identification of IgG1 Aggregation Initiation Region by Hydrogen Deuterium Mass Spectrometry

Antibody aggregates are a potential risk for immunogenicity; therefore, rational approaches to improve associated aggregation properties need to be developed. Here, we report the amino acid region responsible for aggregation initiation. Two types of therapeutic IgG1 antibody monomer samples were prepared: IgG1 mAb40-3M stored at 40°C for 3 months, which existed in monodisperse state, and the monomer mAb65-5m, which was dissociated from small soluble aggregates by heating at 65°C for 5 min. Hydrogen deuterium exchange mass spectrometry of mAb40-3M identified 2 sites in the Fc region (site 1, F239-M256; site 2, S428-G450) with increased exchange rates. Site 1 includes a region reported as being susceptible to structural change induced by stress. Exposure of site 1 was undetected after 2 months of storage at 40°C but was subsequently detectable after 3 months. As site 2 is spatially close to site 1, the structural change of site 1 could propagate site 2. Besides these 2 regions, hydrogen deuterium exchange mass spectrometry of mAb65-5m identified an exposure of I257-W281 in Fc (site 3), within which a peptide sequence with high aggregation tendency was discovered. We thus concluded that exposure of site 3 is a trigger for the association of a partially denatured antibody.     

血清TRAb IgG亚型在甲状腺相关性眼病患者中的特征及临床意义

目的探讨血清TRAb IgG各亚型在不同活动分期甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者中的分布特点,及其在评估TAO活动度中的价值。方法选取2018年8月至2019年2月郑州大学第一附属医院收治的TAO患者43例,依据临床活动度评分(clinical activity score,CAS)进一步分为活动期组(AP组,CAS≥3分,22例)和静止期组(IP组,CAS<3分,21例);Graves病患者(GD组)30例,桥本甲状腺炎患者(HT组)19例,并以同期健康体检者(NC组)50名作为正常对照。收集各组受试者临床基本资料,化学发光免疫法检测血清FT3、FT4、TSH、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)、促甲状腺激素受体抗体(TRAb)水平,酶联免疫吸附法检测血清TRAb IgG和IgG各亚型的百分结合率[binding rate in percentage,(B)],比较各亚型的阳性率和阳性亚型的相对含量。结果(1)与HT组相比,TAO组、GD组IgG1、IgG2阳性率降低,差异有统计学意义(P<0.05)。各疾病组间TRAb IgG亚型相对含量无明显差异(P>0.05)。(2)与IP组相比,AP组IgG1(B)、IgG1阳性率显著升高,IgG4(B)、IgG4相对含量显著降低(P<0.05)。(3)IgG1(B)与TAO活动度呈正相关(B=6.190,P=0.007),IgG4(B)越高越倾向于静止期,但差异无统计学意义(B=-16.390,P=0.052)。(4)活动率评估TAO处于活动期的受试者工作特征(ROC)曲线下面积为0.859(95%CI 0.746~0.973,P<0.05),当活动率为4.29时,约登指数最大,其判断敏感度为81.8%,特异度为81.0%。结论在TAO患者中血清TRAb IgG1水平升高提示疾病趋向活动期,IgG4水平升高提示疾病趋向静止期。活动率可为评估TAO是否处于活动期提供参考依据。     

Aortitis and periaortitis: The puzzling spectrum of inflammatory aortic diseases

Aortitis and periaortitis are inflammatory diseases of the aorta and its main branches; they differ in the extension of inflammation, which is confined to the aortic wall in aortitis, and spreads to the periaortic space in periaortitis. Aortitis is classified as non-infectious or infectious. Non-infectious aortitis represents a common feature of large-vessel vasculitides but can also be isolated or associated with other rheumatologic conditions. Periaortitis can be idiopathic or secondary to a wide array of etiologies such as drugs, infections, malignancies, and other proliferative diseases. Notably, both aortitis and periaortitis may arise in the context of IgG4-related disease, a recently characterised fibro-inflammatory systemic disease. Prompt recognition, correct diagnosis and appropriate treatment are essential in order to avoid life-threatening complications.     

Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.     

Antinuclear antibodies positivity is not rare during multiple sclerosis and is associated with relapsing status and IgG oligoclonal bands positivity

IntroductionAs an immune-mediated disease of the central nervous system, multifaceted aspects of a humoral immune response are widely described during multiple sclerosis (MS). However, the prevalence of different auto-antibodies, such as antinuclear antibodies (ANA), during MS is very variable and their clinical relevance remains controversial. Our aim was to evaluate the prevalence and clinical correlations of ANA positivity in South Tunisian MS patients.Material and methodsWe performed ANA screening using indirect immunofluorescence (IIF) on HEp-2 cells (Biosystems®) in 82 MS patients. For ANA positive samples (titer ≥1/160), anti-ds-DNA detection (IIF on Crithidia luciliae (Biosystems®)) and extractable nuclear antigen typing (immunodot (Euroimmun®)) were performed.ResultsANA were positive in 35/82 MS patients (42.7%). The titer was ≥ 1/320 in 16/35 patients. The antigenic specificity of ANA was identified in 7/35 patients. None of the patients had extra-neurological manifestations. No correlation was found between ANA and age, gender, MS course, disease duration, disability, annual relapse rate nor IgG index. ANA positivity was more frequent in patients with IgG oligoclonal bands (OCB) (47.1%) than in patients without IgG OCB (16,6%) (p = 0.049). Regarding disease activity, ANA positivity was significantly more frequent in patients with relapse (52.6%) than in patients in remission (25.9%) (p = 0.031).ConclusionOur results showed that ANA positivity in MS disease is not rare. This positivity was not associated with clinical expression of any connective tissue disease. ANA occurrence in MS was associated with IgG OCB+ profile and relapsing status, probably reflecting an ongoing immune dysregulation.     

泪腺良性淋巴上皮病变的病理特点及IgG4和C3的表达

目的　探讨IgG4和C3在泪腺良性淋巴上皮病变发生发展中的作用。方法　收集2010年7月至2018年5月就诊于承德医学院附属医院眼科、解放军总医院眼科15例（15眼）泪腺良性淋巴上皮病变患者的泪腺肿物为试验组，10例（10眼）因其他疾病而行眶内容物摘除术的正常泪腺组织标本为对照组。采用HE染色法观察2组泪腺病理形态学变化及其组织病理学特点，采用免疫组织化学染色法检测2组泪腺组织中IgG4、C3的表达，并对二者表达相关性进行分析。结果　HE染色结果显示，对照组泪腺由正常腺泡及导管组成，导管上皮细胞排列整齐，细胞结构清晰，其间有少量的淋巴细胞；试验组泪腺组织中可见大量淋巴细胞、浆细胞浸润，淋巴滤泡形成，其间可见上皮-肌上皮岛结构改变，同时伴有不同程度纤维化。IgG4在试验组阳性表达面积为（30 934.80±16 057.17）像素，对照组阳性表达面积为（325.42±204.43）像素，试验组中明显高于对照组（t=-7.38，P=0.000）；C3在试验组阳性表达面积为（43 169.49±33 206.60）像素，对照组阳性表达面积为（323.24±271.29）像素，试验组中明显高于对照组，差异有统计学意义（t=-5.00，P=0.000）。试验组中IgG4与C3表达无相关性（r=-0.137，P=0.671）。结论　泪腺良性淋巴上皮病变患者的泪腺发生了明确的病理改变，这可能与IgG4和C3在泪腺中的高表达有关。