What is IgG4? A review of the biology of a unique immunoglobulin subtype

Nirula, Ajay; Glaser, Scott; Kalled, Susan L.; Taylor, Frederick R.

doi:10.1097/bor.0b013e3283412fd4

Cited by 286 publications

(224 citation statements)

References 35 publications

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“…Specifically, regulatory T cell-associated cytokines IL-10 and IL-21 are supposed to drive the class switch in B cells to IgG4 and their differentiation into IgG4-secreting plasma cells. 31,32 In this context, it was intriguing to study the abundance of regulatory T cells in IgG4-positive primary cutaneous marginal zone lymphomas in comparison with nonIgG4 primary cutaneous marginal zone lymphomas. The finding that the content of FOXP3-positive regulatory T cells did not differ among IgA-, IgG1-3-, and IgG4-positive primary cutaneous marginal zone lymphomas, whereas it was significantly lower in IgM-positive primary cutaneous marginal zone lymphomas in our series, has several implications.…”

Section: Discussionmentioning

confidence: 99%

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

et al. 2013

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The expression of IgG4 in malignant B-cell lymphomas has only partially been studied. Recent reports described single cases of marginal zone lymphomas arising in the ocular adnexae that express IgG4. Moreover, a subset of dura-associated marginal zone lymphomas appear to express IgG4 as well. We investigated IgG4 expression in a more systematic manner in a large cohort of marginal zone lymphoma specimens derived from the archive of our institute. Overall, we examined 169 marginal zone lymphomas of various primary sites that displayed a distinct plasmacytic differentiation and light chain restriction, allowing for a detailed investigation of the immunoglobulin heavy chain expression in these tumors by immunohistochemistry. Unexpectedly, primary cutaneous marginal zone lymphomas showed frequent IgG4 expression. Although only 1 out of 120 noncutaneous marginal zone lymphomas, located in the ocular adnexae, expressed IgG4, 19 of 49 (39%) primary cutaneous marginal zone lymphomas showed this feature, constituting the highest expression rate of IgG4 reported to date in any B-cell lymphoma. None of the IgG4-positive cutaneous marginal zone lymphomas with available clinical data showed evidence of a preexisting systemic IgG4-related disease, suggesting a localized immunologic IgG4-driven pathogenetic process at early stages of the disease. IgG4-positive and IgG4-negative primary cutaneous marginal zone lymphomas did not significantly differ in architectural features of the infiltrate or the composition of the reactive T-cell infiltrate as determined by analysis of T-cell content, CD4/CD8 ratio, and content of FOXP3-and PD1-positive T cells. Although the pathogenetic role of IgG4 expression in a significant subset of primary cutaneous marginal zone lymphomas with plasmacytic differentiation remains unclear at present, the demonstration of IgG4 expression in a marginal zone lymphoma involving the skin might be a helpful clue in the routine diagnostic setting, as these tumors will almost invariably be of primary cutaneous origin with an extremely low risk of spread to noncutaneous sites and an excellent prognosis.

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Section: Discussionmentioning

confidence: 99%

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

et al. 2013

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“…It is unclear whether the IgG4-positive plasma cells are causative of the pathological process seen, or are only a marker for an as-yet undescribed etiology or etiologies. 6 In spite of this, the recognition of IgG4-related diseases and related lymphadenopathy is of increasing importance. Because IgG4-related sclerosing disease is systemic and progressive, timely diagnosis is critical.…”

Section: Discussionmentioning

confidence: 99%

“…Ten cases had concurrent flow cytometry results on the lymph node specimens (Cases 2, 5,6,8,11,14,15,16,23,25). In all ten cases, CD4-positive T cells were increased compared with CD8 cells with CD4:CD8 ratios ranging from 3.36 to 11.24.…”

Section: Flow Cytometrymentioning

confidence: 99%

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Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells

et al. 2012

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“…IgG4 normally comprises only 3-6% of total IgG, has a low affinity for the target antigen, is unable to bind C1q complement, and is Th2 dependent (41)(42)(43). During acute phase(s) of IgG4-related systemic disease, IgG4 is typically elevated.…”

Section: Discussionmentioning

confidence: 99%

A 45‐year‐old man with flank pain and inability to ejaculate

Muskardin

Gertner

2012

Arthritis Care & Research

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A 45-year-old man with left-sided flank pain and difficulty ejaculating. History of the Present IllnessThe patient developed left-sided flank pain in April 2010. He was evaluated in the emergency department when the pain had persisted for 3 weeks. He reported worsening of the pain in the evening and difficulty with ejaculation since the pain began: "I get a knot in my side," then "I can't ejaculate." He also reported associated low back pain and increased pain with bending to his left. His general physical examination was unremarkable. Urine analysis demonstrated 30 mg/dl protein, 10 mg/dl ketones, 8 mg/dl urobilinogen (reference value Ͻ2.0), 8 red blood cells/ high-power field (hpf), 2 white blood cells/hpf, and mucous. He was prescribed ibuprofen for abdominal pain and was advised to follow up with his primary care provider.The pain persisted. He saw his primary provider in July with worsening epigastric and left-sided abdominal and flank pain. By this time, he had decreased appetite, early satiety, and weight loss of 22 pounds. His primary provider ordered a computed tomographic (CT) scan of his abdomen and pelvis, which demonstrated a rind of soft tissue in the retroperitoneum surrounding the aorta and inferior vena cava and wall thickening of the sigmoid colon and rectum. A biopsy of the mass was done by interventional radiology at another hospital. Since his pain was unrelieved by acetaminophen/hydrocodone, he was admitted to our hospital for further evaluation and pain control. He did not know the results of the biopsy. Medical HistoryHe had been relatively healthy prior to the onset of illness in April. Atheromatous calcification of the aorta with mild ectasia inferiorly measuring up to 2.3 cm in diameter was noted incidentally on a CT scan obtained to evaluate for ureteral calculi in September 2008. He had a remote history of gonorrhea and chlamydia infections, which were treated. He had been seen in the emergency department for right testicular pain following trauma at age 35 years and left testicular pain without clear etiology at ages 40 and 43 years. The first episode of left testicular pain was attributed to epididymitis. The second was attributed to suspected passage of a ureteral calculus. Social and Family HistoryThe patient's family history was negative for rheumatic disorders. Several family members, including his mother, had diabetes mellitus and hypertension. His sister had thyroid disease. He was unemployed, but previously worked as a baker. He smoked one-quarter of a pack of cigarettes per day for several years, and previously smoked marijuana. He consumed, on average, 1 alcoholic beverage per week and denied intravenous drug use. He was sexually active and did not consistently use barrier protection. Review of SystemsThe patient reported persistent inability to ejaculate, without decrease in arousal or orgasm and without associated pain. He also reported low back pain that preceded his current illness by years. He had constipation for 2 weeks.

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What is IgG4? A review of the biology of a unique immunoglobulin subtype

Abstract: IgG4 is a unique antibody biologically and structurally. Increased understanding of its precise role in the clinical syndromes that comprise IgG4-RSD may ultimately elucidate the underlying pathogenesis.

Cited by 286 publications

References 35 publications

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells

A 45‐year‐old man with flank pain and inability to ejaculate

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