CD123 differentiates acute GVHD from infections, drug reactions

CD123 expression in the intestinal mucosa may be a useful immunohistochemical marker to differentiate acute colonic graft-versus-host disease in hematopoietic stem-cell transplant patients who develop nonspecific gastrointestinal symptoms, according to Dr. Jingmei Lin and her colleagues.

Immunostaining endoscopic biopsy samples with CD123, an interleukin-3 receptor subunit, can identify plasmacytoid dendritic cells that are critical to the development of graft-versus-host disease (GVHD) but are not known to be present in infectious processes, adverse drug reactions, or chemoradiation toxicities. CD123 immunostaining was associated with a sensitivity of 66% and a specificity of 97% for acute GVHD, the researchers said (Hum. Pathol. 2013 June 21 [doi:10.1016/j.humpath.2013.02.023]).

Gastrointestinal GVHD can present as a variety of nonspecific symptoms and can be difficult to distinguish pathologically from colonic cytomegaloivrus, a major complication following stem-cell transplantation. Gastrointestinal GVHD also can be hard to differentiate pathologically from other opportunistic infections, such as Clostridium difficile and adenovirus infections, as well as from adverse reactions to chemotherapy and radiation. Early distinction is crucial because treatment approaches differ for these three entities and because early therapy improves outcomes for acute GVHD, said Dr. Lin of the departments of pathology and laboratory medicine, Indiana University, Indianapolis, and her associates.

The researchers reviewed 38 colonic endoscopy samples from stem-cell transplant recipients known to have gastrointestinal GVHD and compared them with 14 samples from patients who had not undergone transplantation and who were known to have cytomegalovirus colitis.

The researchers also assessed 11 biopsy samples (colon, stomach, small bowel, and esophagus) from patients who had taken mycophenolate, which is used for the prophylaxis of GVHD. They additionally assessed 47 biopsies (upper and lower GI) from patients who had undergone hematopoietic stem-cell transplantation but had not developed GVHD or infection, and 5 colon biopsies from control subjects.

All of the GVHD patients had presented with nonspecific symptoms of diarrhea, abdominal pain, abdominal cramping, nausea, and/or vomiting.

Among the 38 samples from patients with acute GVHD, 25 (66%) were positive on CD123 staining, showing plasmacytoid dendritic cells in the lamina propria. This marker increased in sensitivity as lesion grade increased: 60% of grade-1 and grade-2 lesions were positive, compared with 72% of grade-3 and grade-4 lesions.

In contrast, 2 of the 14 (14%) samples from patients with CMV, none of the 47 samples from transplant patients without GVHD, none of the 11 samples from patients who took mycophenolate, and none of the 5 control samples were positive for CD123.

The investigators said that they have no funding or conflicts of interest to disclose.

CD123 expression in the intestinal mucosa may be a useful immunohistochemical marker to differentiate acute colonic graft-versus-host disease in hematopoietic stem-cell transplant patients who develop nonspecific gastrointestinal symptoms, according to Dr. Jingmei Lin and her colleagues.

Immunostaining endoscopic biopsy samples with CD123, an interleukin-3 receptor subunit, can identify plasmacytoid dendritic cells that are critical to the development of graft-versus-host disease (GVHD) but are not known to be present in infectious processes, adverse drug reactions, or chemoradiation toxicities. CD123 immunostaining was associated with a sensitivity of 66% and a specificity of 97% for acute GVHD, the researchers said (Hum. Pathol. 2013 June 21 [doi:10.1016/j.humpath.2013.02.023]).

Gastrointestinal GVHD can present as a variety of nonspecific symptoms and can be difficult to distinguish pathologically from colonic cytomegaloivrus, a major complication following stem-cell transplantation. Gastrointestinal GVHD also can be hard to differentiate pathologically from other opportunistic infections, such as Clostridium difficile and adenovirus infections, as well as from adverse reactions to chemotherapy and radiation. Early distinction is crucial because treatment approaches differ for these three entities and because early therapy improves outcomes for acute GVHD, said Dr. Lin of the departments of pathology and laboratory medicine, Indiana University, Indianapolis, and her associates.

The researchers reviewed 38 colonic endoscopy samples from stem-cell transplant recipients known to have gastrointestinal GVHD and compared them with 14 samples from patients who had not undergone transplantation and who were known to have cytomegalovirus colitis.

The researchers also assessed 11 biopsy samples (colon, stomach, small bowel, and esophagus) from patients who had taken mycophenolate, which is used for the prophylaxis of GVHD. They additionally assessed 47 biopsies (upper and lower GI) from patients who had undergone hematopoietic stem-cell transplantation but had not developed GVHD or infection, and 5 colon biopsies from control subjects.

All of the GVHD patients had presented with nonspecific symptoms of diarrhea, abdominal pain, abdominal cramping, nausea, and/or vomiting.

Among the 38 samples from patients with acute GVHD, 25 (66%) were positive on CD123 staining, showing plasmacytoid dendritic cells in the lamina propria. This marker increased in sensitivity as lesion grade increased: 60% of grade-1 and grade-2 lesions were positive, compared with 72% of grade-3 and grade-4 lesions.

In contrast, 2 of the 14 (14%) samples from patients with CMV, none of the 47 samples from transplant patients without GVHD, none of the 11 samples from patients who took mycophenolate, and none of the 5 control samples were positive for CD123.

The investigators said that they have no funding or conflicts of interest to disclose.

CD123 expression in the intestinal mucosa may be a useful immunohistochemical marker to differentiate acute colonic graft-versus-host disease in hematopoietic stem-cell transplant patients who develop nonspecific gastrointestinal symptoms, according to Dr. Jingmei Lin and her colleagues.

Immunostaining endoscopic biopsy samples with CD123, an interleukin-3 receptor subunit, can identify plasmacytoid dendritic cells that are critical to the development of graft-versus-host disease (GVHD) but are not known to be present in infectious processes, adverse drug reactions, or chemoradiation toxicities. CD123 immunostaining was associated with a sensitivity of 66% and a specificity of 97% for acute GVHD, the researchers said (Hum. Pathol. 2013 June 21 [doi:10.1016/j.humpath.2013.02.023]).

Gastrointestinal GVHD can present as a variety of nonspecific symptoms and can be difficult to distinguish pathologically from colonic cytomegaloivrus, a major complication following stem-cell transplantation. Gastrointestinal GVHD also can be hard to differentiate pathologically from other opportunistic infections, such as Clostridium difficile and adenovirus infections, as well as from adverse reactions to chemotherapy and radiation. Early distinction is crucial because treatment approaches differ for these three entities and because early therapy improves outcomes for acute GVHD, said Dr. Lin of the departments of pathology and laboratory medicine, Indiana University, Indianapolis, and her associates.

The researchers reviewed 38 colonic endoscopy samples from stem-cell transplant recipients known to have gastrointestinal GVHD and compared them with 14 samples from patients who had not undergone transplantation and who were known to have cytomegalovirus colitis.

The researchers also assessed 11 biopsy samples (colon, stomach, small bowel, and esophagus) from patients who had taken mycophenolate, which is used for the prophylaxis of GVHD. They additionally assessed 47 biopsies (upper and lower GI) from patients who had undergone hematopoietic stem-cell transplantation but had not developed GVHD or infection, and 5 colon biopsies from control subjects.

All of the GVHD patients had presented with nonspecific symptoms of diarrhea, abdominal pain, abdominal cramping, nausea, and/or vomiting.

Among the 38 samples from patients with acute GVHD, 25 (66%) were positive on CD123 staining, showing plasmacytoid dendritic cells in the lamina propria. This marker increased in sensitivity as lesion grade increased: 60% of grade-1 and grade-2 lesions were positive, compared with 72% of grade-3 and grade-4 lesions.

In contrast, 2 of the 14 (14%) samples from patients with CMV, none of the 47 samples from transplant patients without GVHD, none of the 11 samples from patients who took mycophenolate, and none of the 5 control samples were positive for CD123.

The investigators said that they have no funding or conflicts of interest to disclose.