Berti Alvise, Della-Torre Emanuel, Gallivanone Francesca, Canevari Carla, Milani Raffaella, Lanzillotta Marco, Campochiaro Corrado, Ramirez Giuseppe Alvise, Bozzalla Cassione Emanuele, Bozzolo Enrica, Pedica Federica, Castiglioni Isabella, Arcidiacono Paolo Giorgio, Balzano Gianpaolo, Falconi Massimo, Gianolli Luigi, Dagna Lorenzo
IRCCS San Raffaele Scientific Institute, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Milan.
Milan, IRCCS San Raffaele Scientific Institute, Università Vita-Salute San Raffaele.
Rheumatology (Oxford). 2017 Dec 1;56(12):2084-2092. doi: 10.1093/rheumatology/kex234.
[18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity.
Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation.
Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal < 3). Serum IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P < 0.05 for all comparisons).
18F-FDG uptake of IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation.
[18F]氟脱氧葡萄糖（18F-FDG）PET/CT越来越多地用于评估IgG4相关性疾病（IgG4-RD）的器官受累情况及对治疗的反应，但18F-FDG摄取与疾病活动之间尚未建立明确的相关性。我们旨在将18F-FDG摄取的强度和分布与IgG4-RD活动经过验证的临床、血清学和免疫学参数相关联。
20例活动性IgG4-RD患者接受了基线18F-FDG PET/CT检查。10例患者在免疫抑制治疗后重复进行了18F-FDG PET/CT检查。使用校正了部分容积效应（PVC）的标准化摄取值（PVC-SUV）以及有（TLGtot+ln）和无（TLGtot-ln）淋巴结的总病灶糖酵解（TLG）来测量18F-FDG组织摄取。通过临床参数[IgG4-RD反应指数（RI）]、血清学（ESR和CRP）和免疫学（血清IgG4和循环浆母细胞）生物标志物评估疾病活动。将增强肝纤维化评分用作成纤维细胞活化的生物标志物。
13例（65%）患者有两个或更多器官受IgG4-RD影响。所有患者均为活动性IgG4-RD，IgG4-RD RI中位数为9（范围6-15；正常<3）。85%的患者血清IgG4和浆母细胞升高。循环浆母细胞与PVC-SUV呈正相关（P = 0.027），与TLGtot-ln呈负相关（P = 0.023），与TLGtot+ln无相关性（P>0.05）。未发现PVC-SUV或TLG与IgG4-RD RI、ESR、CRP、血清IgG4或增强肝纤维化评分之间存在统计学显著相关性（P>0.05）。免疫抑制治疗的临床反应与循环浆母细胞、PVC-SUV、TLGtot+ln和TLGtot-ln值的一致降低相关（所有比较P<0.05）。
IgG4-RD病灶的18F-FDG摄取反映了B细胞区室的免疫扰动，而非成纤维细胞活化和细胞外基质沉积。疾病活动的传统生物标志物，即IgG4-RD RI、ESR、CRP和血清IgG4水平，似乎与IgG4-RD病灶的放射性代谢活性无相关性。根据我们的结果，PET/CT是评估IgG4-RD活动的可靠工具，尽管淋巴结摄取值得仔细解读。
